$A)$ Cross over during prophase I of meiosis
$B)$ separate during the first mitotic division
$C)$ are produced during $S$ phase between cell divisions
$D)$ cross over during prophase II of meiosis
$E)$ are also called homologous chromosomes
- $A$ is incorrect because it's nonsister chromatids that cross over
- $B$ is incorrect because they separate during the second mitotic division
- Don't know about choice $C$
- $D$ is incorrect because there is no crossing over during Meiosis II
- $E$ is incorrect because well… it's just not true
So is the answer $C$?
It is C. During S-phase the DNA of each chromosome duplicate and the two sister chromatids formed get attached by cohesin proteins. These sister chromatids separate at Anaphase-II of Meiosis.
A sister chromatid refers to either of the two identical copies (chromatids) formed by the replication of a single chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said as 'one-half' of the duplicated chromosome. A full set of sister chromatids is created during the synthesis (S) phase of interphase, when all the chromosomes in a cell are replicated.
Frequent and Efficient Use of the Sister Chromatid for DNA Double-Strand Break Repair during Budding Yeast Meiosis
Recombination between homologous chromosomes of different parental origin (homologs) is necessary for their accurate segregation during meiosis. It has been suggested that meiotic inter-homolog recombination is promoted by a barrier to inter-sister-chromatid recombination, imposed by meiosis-specific components of the chromosome axis. Consistent with this, measures of Holliday junction–containing recombination intermediates (joint molecules [JMs]) show a strong bias towards inter-homolog and against inter-sister JMs. However, recombination between sister chromatids also has an important role in meiosis. The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions, and meiotic double-strand breaks (DSBs) that form within such polymorphic regions must be repaired by inter-sister recombination. Efforts to study inter-sister recombination during meiosis, in particular to determine recombination frequencies and mechanisms, have been constrained by the inability to monitor the products of inter-sister recombination. We present here molecular-level studies of inter-sister recombination during budding yeast meiosis. We examined events initiated by DSBs in regions that lack corresponding sequences on the homolog, and show that these DSBs are efficiently repaired by inter-sister recombination. This occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold) yields of JMs. Loss of the meiotic-chromosome-axis-associated kinase Mek1 accelerates inter-sister DSB repair and markedly increases inter-sister JM frequencies. Furthermore, inter-sister JMs formed in mek1Δ mutants are preferentially lost, while inter-homolog JMs are maintained. These findings indicate that inter-sister recombination occurs frequently during budding yeast meiosis, with the possibility that up to one-third of all recombination events occur between sister chromatids. We suggest that a Mek1-dependent reduction in the rate of inter-sister repair, combined with the destabilization of inter-sister JMs, promotes inter-homolog recombination while retaining the capacity for inter-sister recombination when inter-homolog recombination is not possible.
79 Meiosis II
In some species, cells enter a brief interphase, or interkinesis, before entering meiosis II. Interkinesis lacks an S phase, so chromosomes are not duplicated. The two cells produced in meiosis I go through the events of meiosis II at the same time. During meiosis II, the sister chromatids within the two daughter cells separate, forming four new haploid gametes, each with one copy of each chromosome. The mechanics of meiosis II is similar to mitosis, except that each dividing cell has only one set of homologous chromosomes. Therefore, each cell has half the number of sister chromatids to separate out as a diploid cell undergoing mitosis.
During meiosis II, each sister chromatid is attached to spindle fiber microtubules from opposite poles. The sister chromatids are pulled apart by the spindle fiber microtubules and move toward opposite poles (Figure 1).Figure 1 In prometaphase I, microtubules attach to the fused kinetochores of homologous chromosomes. In anaphase I, the homologous chromosomes are separated. In prometaphase II, microtubules attach to individual kinetochores of sister chromatids. In anaphase II, the sister chromatids are separated.
The chromosomes arrive at opposite ends of the cells and begin to decondense (unwind). Nuclear envelopes form around the chromosomes. Cytokinesis separates the two cells into four unique haploid cells. At this point, the newly formed nuclei are both haploid and have only one copy of the single set of chromosomes. The cells produced are genetically unique because of the random assortment of paternal and maternal homologs and because of the recombining of maternal and paternal segments of chromosomes (with their sets of genes) that occurs during crossover.
The entire process of meiosis is outlined in Figure 2 (you do not need to know the names of the phases or what happens during each phase, only what happens overall during meiosis I and II).
Figure 2 An animal cell with a diploid number of four (2n = 4) proceeds through the stages of meiosis to form four haploid daughter cells.
Sister chromatids during meiosis - Biology
Unit Three. The Continuity of Life
9.3. The Stages of Meiosis
Now, let’s look more closely at the process of meiosis. Meiosis consists of two rounds of cell division, called meiosis I and meiosis II, which produce four haploid cells. Just as in mitosis, the chromosomes have replicated before meiosis begins, during a period called interphase. The first of the two divisions of meiosis, called meiosis I (meiosis I is shown in the outer circle of the Key Biological Process illustration on the facing page), serves to separate the two versions of each chromosome (the homologous chromosomes or homologues) the second division, meiosis II (the inner circle), serves to separate the two replicas of each version, called sister chromatids. Thus when meiosis is complete, what started out as one diploid cell ends up as four haploid cells. Because there was one replication of DNA but two cell divisions, the process reduces the number of chromosomes by half.
Meiosis I is traditionally divided into four stages:
1. Prophase I. The two versions of each chromosome (the two homologues) pair up and exchange segments.
2. Metaphase I. The chromosomes align on a central plane.
3. Anaphase I. One homologue with its two sister chromatids still attached moves to a pole of the cell, and the other homologue moves to the opposite pole.
4. Telophase I. Individual chromosomes gather together at each of the two poles.
In prophase I, individual chromosomes first become visible, as viewed with a light microscope, as their DNA coils more and more tightly. Because the chromosomes (DNA) have replicated before the onset of meiosis, each of the threadlike chromosomes actually consists of two sister chromatids associated along their lengths (held together by cohesin proteins in a process called sister chromatid cohesion) and joined at their centromeres, just as in mitosis. However, now meiosis begins to differ from mitosis. During prophase I, the two homologous chromosomes line up side by side, physically touching one another, as you see in figure 9.5. It is at this point that a process called crossing over is initiated, in which DNA is exchanged between the two nonsister chromatids of homologous chromosomes. The chromosomes actually break in the same place on both nonsister chromatids and sections of chromosomes are swapped between the homologous chromosomes, producing a hybrid chromosome that is part maternal chromosome (the green sections) and part paternal chromosome (the purple sections). Two elements hold the homologous chromosomes together: (1) cohesion between sister chromatids and (2) crossovers between nonsister chromatids (homologues). Late in prophase, the nuclear envelope disperses.
In crossing over, the two homologues of each chromosome exchange portions. During the crossing over process, nonsister chromatids that are next to each other exchange chromosome arms or segments.
In metaphase I, the spindle apparatus forms, but because homologues are held close together by crossovers, spindle fibers can attach to only the outward-facing kinetochore of each centromere. For each pair of homologues, the orientation on the metaphase plate is random which homologue is oriented toward which pole is a matter of chance. Like shuffling a deck of cards, many combinations are possible—in fact, 2 raised to a power equal to the number of chromosome pairs. For example, in a hypothetical cell that has three chromosome pairs, there are eight possible orientations (2 3 ). Each orientation results in gametes with different combinations of parental chromosomes. This process is called independent assortment. The chromosomes in figure 9.6 line up along the metaphase plate, but whether the maternal chromosome (the green chromosomes) is on the right or left of the plate is completely random.
Figure 9.6. Independent assortment.
Independent assortment occurs because the orientation of chromosomes on the metaphase plate is random. Shown here are four possible orientations of chromosomes in a hypothetical cell. Each of the many possible orientations results in gametes with different combinations of parental chromosomes.
In anaphase I, the spindle attachment is complete, and homologues are pulled apart and move toward opposite poles. Sister chromatids are not separated at this stage. Because the orientation along the spindle equator is random, the chromosome that a pole receives from each pair of homologues is also random with respect to all chromosome pairs. At the end of anaphase I, each pole has half as many chromosomes as were present in the cell when meiosis began. Remember that the chromosomes replicated and thus contained two sister chromatids before the start of meiosis, but sister chromatids are not counted as separate chromosomes. As in mitosis, count the number of centromeres to determine the number of chromosomes.
In telophase I, the chromosomes gather at their respective poles to form two chromosome clusters. After an interval of variable length, meiosis II occurs in which the sister chromatids are separated as in mitosis. Meiosis can be thought of as two consecutive cycles, as shown in the Key Biological Process illustration on the previous page. The outer cycle contains the phases of meiosis I and the inner cycle contains the phases of meiosis II, discussed next.
After a brief interphase, in which no DNA synthesis occurs, the second meiotic division begins. Meiosis II is simply a mitotic division involving the products of meiosis I, except that the sister chromatids are not genetically identical, as they are in mitosis, because of crossing over. You can see this by looking at figure 9.7, where some of the arms of the sister chromatids contain two different colors. At the end of anaphase I, each pole has a haploid complement of chromosomes, each of which is still composed of two sister chromatids attached at the centromere. Like meiosis I, meiosis II is divided into four stages:
1. Prophase II. At the two poles of the cell, the clusters of chromosomes enter a brief prophase II, where a new spindle forms.
2. Metaphase II. In metaphase II, spindle fibers bind to both sides of the centromeres and the chromosomes line up along a central plane.
3. Anaphase II. The spindle fibers shorten, splitting the centromeres and moving the sister chromatids to opposite poles.
4. Telophase II. Finally, the nuclear envelope re-forms around the four sets of daughter chromosomes.
The main outcome of the four stages of meiosis II— prophase II, metaphase II, anaphase II, and telophase II—is to separate the sister chromatids. The final result of this division is four cells containing haploid sets of chromosomes. No two are alike because of the crossing over in prophase I. The nuclei are then reorganized, and nuclear envelopes form around each haploid set of chromosomes. The cells that contain these haploid nuclei may develop directly into gametes, as they do in most animals. Alternatively, they may themselves divide mitotically, as they do in plants, fungi, and many protists, eventually producing greater numbers of gametes or, as in the case of some plants and insects, adult haploid individuals.
The Important Role of Crossing Over
If you think about it, the key to meiosis is that the sister chromatids of each chromosome are not separated from each other in the first division. Why not? What prevents microtubules from attaching to them and pulling them to opposite poles of the cell, just as eventually happens later in the second meiotic division? The answer is the crossing over that occurred early in the first division. By exchanging segments, the two homologues are tied together by strands of DNA. It is because microtubules can gain access to only one side of each homologue that they cannot pull the two sister chromatids apart! Imagine two people dancing closely—you can tie a rope to the back of each person’s belt, but you cannot tie a second rope to their belt buckles because the two dancers are facing each other and are very close. In just the same way, microtubules cannot attach to the inner sides of the homologues because crossing over holds the homologous chromosomes together like dancing partners.
Key Learning Outcome 9.3. During meiosis I, homologous chromosomes move to opposite poles of the cell. At the end of meiosis II, each of the four haploid cells contains one copy of every chromosome in the set, rather than two. Because of crossing over, no two cells are the same.
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Genetic Variation During Meiosis
Practice: Which of the following processes occurs when homologous chromosomes cross over in meiosis I?
a) Two sister chromatids get tangled, resulting in one re-sequencing its DNA.
b) Two sister chromatids exchange identical pieces of DNA.
c) Maternal alleles are "corrected" to be like paternal alleles and vice versa.
d) Corresponding segments of non-sister chromatids from homologous chromosomes are exchanged.
Practice: Crossing over involves each of the following EXCEPT:
a) The transfer of DNA between two non-sister chromatids.
b) The transfer of DNA between two sister chromatids.
c) The formation of a synaptonemal complex.
d) The alignment of homologous chromosomes.
e) All of the above are involved in crossing over.
Concept #2: Independent Assortment
Example #1: For a species with a haploid number of 23 chromosomes, how many combinations of maternal and paternal chromosomes are possible for the gametes based on the independent assortment of chromosomes during meiosis?
Practice: How many genetically unique gametes can be created in an organism with 4 chromosomes?
Practice: During which of the following processes does independent assortment of chromosomes occur?
c) In mitosis and meiosis I.
d) In mitosis and meiosis II.
e) In meiosis I and meiosis II.
Practice: Independent assortment of chromosomes is a result of which of the following processes?
a) The random way each pair of homologous chromosomes lines up at the metaphase plate.
b) The random combinations of eggs and sperm during fertilization.
c) The random distribution of the sister chromatids into the two daughter cells.
d) The diverse combination of alleles that may be found within any given chromosome.
Patricia Wadsworth , Nasser M. Rusan , in Encyclopedia of Biological Chemistry , 2004
During anaphase, sister chromatids separate and move to the spindle poles ( Figures 2 and 3 ). Anaphase consists of two phases, anaphase A and B. During anaphase A, the chromosomes move to the poles and kinetochore fiber microtubules shorten during anaphase B, the spindle poles move apart as interpolar microtubules elongate and slide past one another. Many cells undergo both anaphase A and B motions, but in some cases one or the other motion dominates.
Separation of the paired sister chromatids is required for poleward motion in anaphase. Chromatid separation results from the proteolytic degradation of components that link the chromatids at the centromere. Degradation is triggered by the activity of the anaphase-promoting complex, which regulates cell cycle progression. Chromatid separation is not the result of tugging by microtubules and motor proteins, and can be observed even in the absence of microtubules.
Although the motion of the chromosomes to the spindle poles in anaphase has fascinated biologists for many years, the molecular basis for this motion remains controversial and incompletely understood. During anaphase A, kinetochore microtubules must shorten as the chromosomes move poleward. Measurements of spindle flux show that subunit loss from microtubules occurs at the spindle poles during anaphase. In many cells, however, the rate that chromosomes move exceeds the rate of subunit loss at the pole, and thus subunit loss must also occur at the kinetochore.
Pioneering studies of mitosis in living embryonic cells demonstrated that assembly and disassembly of microtubule polymers result in chromosome motion. This work led to the hypothesis that microtubule disassembly drives chromosome motion. Later work identified molecular motors at the kinetochore, leading to the alternative hypothesis that forces generated by molecular motors drive chromosome motion. One possibility is that molecular motors power chromosome motion, but the rate of chromosome motion is limited by kinetochore microtubule disassembly. Alternatively, disassembly may be responsible for chromosome motion, and motors may tether the chromosomes to the shortening fiber. The presence of potentially redundant mechanisms for chromosome motion may reflect the fact that mitotic fidelity is of utmost importance.
Proper chromosome segregation during mitotic cell division requires at least two chromosome-associated protein complexes. At the centromere, functional kinetochores must be formed on individual sister chromatids to facilitate the attachment of the chromatids to opposite spindle poles. In addition, cohesion must be established between the centromeres and along the arms of the sister chromatids and maintained until anaphase to prevent their precocious separation.
By comparison with mitotic cell division, the segregation behavior of chromosomes during meiotic cell division is complex, necessitating modification of both the kinetochore and cohesion complexes. Our understanding of these meiotic modifications remains rudimentary. The first meiotic division (MI) involves the segregation of homologs rather than sister chromatids (Fig. 1A). Thus, successful chromosome segregation at MI requires specialized cohesion mechanisms that provide physical connections between homologs (rather than sister chromatids), and impose constraint on the centromeres of sister chromatids so that their kinetochores form attachments to the same rather than opposing spindle poles. The second meiotic division (MII) is similar to a mitotic cell division, involving the segregation of sister chromatids. However, because MI and MII occur without an intervening S phase, successful chromosome segregation at MII requires a mechanism whereby cohesion is released along the chromosome arms at anaphase I but maintained between sister centromeres until anaphase II.
It is commonly assumed that the specialized meiotic cohesion requirements depend upon the unique events of meiotic prophase, e.g. synapsis and recombination. The role of recombination in the disjunction of homologous chromosomes at MI is well established (e.g. Carpenter, 1994 reviewed in Hassold et al., 2000 Hawley, 1988 Koehler et al., 1996 Lamb et al., 1996). The role of synapsis remains less well characterized, but the inferential evidence is compelling: both defects in homolog synapsis and the absence of a homologous partner are associated with an increased frequency of premature separation of sister chromatids at MI in a variety of species (reviewed in Moore and Orr-Weaver, 1998 Wolf, 1993). Moreover studies in corn, yeast and mammals provide evidence for the involvement of components of the synaptonemal complex (SC), the proteinaceous structure involved in homolog synapsis, in MI segregation. In maize, the analysis of a variety of mutants and structural rearrangements provides compelling evidence for a relationship between the SC and sister chromatid cohesion and suggests a direct correlation between synaptic failure in the centromeric region and precocious sister chromatid segregation (PSCS) (reviewed in Maguire, 1995). In yeast, mutations in the meiosis-specific component of the cohesion complex, Rec8, show an increase in PSCS at MI (Watanabe and Nurse, 1999). Finally, in mammals, two pieces of data implicate the involvement of SC proteins in meiotic sister chromatid cohesion. First, remnants of the lateral element persist at the centromere until anaphase II, as revealed by immunolocalization studies using antibodies to two protein components, SCP3 and SCP2 (Dobson et al., 1994 Offenberg et al., 1998). Second, studies of the recently identified cohesin components, SMC1 and SMC3, provide evidence of interactions with SCP3 and SCP2 (Eijpe et al., 2000). Thus, there is considerable indirect evidence for the involvement of SC proteins in the unique behavior of sister kinetochores at MI, in the maintenance of connections between homologs, and in the maintenance of cohesion between sister centromeres until anaphase II. However, the mechanistic details remain unclear.
These processes are not only of academic interest to students of meiotic cell division but rather have a dramatic impact on human life: the meiotic divisions in the human female are extraordinarily error prone. Estimates of the error frequency range from one in twenty to one in three human oocytes, depending upon the age of the woman (reviewed in Hassold et al., 1996). Despite intensive investigation, the reason for the high error rate in our species remains unknown. It is clear, however, that the majority of errors occur during the first meiotic division, that the propensity for segregation errors is chromosome-specific, and that the fidelity of chromosome segregation is influenced by the number and placement of recombination events along the chromosome arms (reviewed in Hassold et al., 2000). It has been postulated that PSCS is a major mechanism responsible for the age-related increase in segregation errors in our species (Angell, 1997 Angell et al., 1994 Wolstenholme and Angell, 2000), and the small amount of data available from direct studies of human oocytes are consistent with this suggestion (Angell, 1997 Angell et al., 1994 Mahmood et al., 2000 Volarcik et al., 1998).
Studies of human nondisjunction have been limited both by the difficulty of obtaining human oocytes and the lack of a suitable animal model for experimental studies aimed at understanding the age effect in our species. However, the high degree of conservation among species in proteins that mediate some of the specialized meiotic chromosome behaviors suggests that the mouse may provide valuable mechanistic insight to human aneuploidy. Accordingly, we have utilized the female XO mouse to study the factors that influence PSCS at MI. As in other organisms (reviewed in Wolf, 1993), the sister chromatids of the univalent X segregate at anaphase of MI in a proportion of cells (Hunt et al., 1995) however, the frequency of PSCS versus ‘intact’ segregation (i.e. in which the sister chromatids of the univalent remain attached) is influenced by genetic background (LeMaire-Adkins and Hunt, 2000). This difference in MI segregation on two inbred backgrounds provides a genetic approach to understanding the factors that influence the behavior of sister kinetochores at the first meiotic division. We report here the results of detailed meiotic studies that exclude X-chromosome specific differences and suggest that segregation is influenced by the action of an autosomal gene or genes. We hypothesized that this trans-acting factor(s) would influence the synaptic behavior of the X chromosome, and that failure to undergo self-synapsis involving the centromere of the chromosome would result in the premature separation of X chromatids at MI. Our observations did not fit this expectation, but our studies provide new insight to the complexity of the synaptic process and suggest that inferences about subsequent meiotic events based on pachytene analysis may be misleading. More importantly, however, our efforts to correlate segregation behavior with the retention of synaptonemal complex proteins revealed a surprising difference in centromere-associated proteins between oogenesis and spermatogenesis. Differences in the protein components of the meiotic chromosome cohesion complex may influence the fidelity of meiotic chromosome segregation, thus this intriguing sexual dimorphism may provide a partial explanation for the high chromosome error rate during human female meiosis.
Meiosis is a process that starts with a given number of chromosomes in the nucleus of a cell, and ends with gamete cells that each contain half the number of chromosomes that were in the original cell. Most human cells, for example, have 46 chromosomes, whereas sperm and egg cells have only 23 chromosomes. In the early stages of meiosis, the process of replication copies the DNA to produce chromosomes with two sister chromatids (see Figure 1). The next stage is for chromosomes with similar sequences, called homologs, to form pairs and exchange DNA in a process called recombination. The chromosomes then undergo two rounds of segregation to complete the process. Ensuring that all these steps occur in the correct order is clearly vital for successful meiosis. Now, in eLife, Matthew Miller, Elçin Ünal and Angelika Amon of MIT, working with Gloria Brar of UCSF, reveal the mechanisms used by cells to ensure that meiosis proceeds as nature intended (Miller et al., 2012).
The different stages of meiosis. In this illustration the cell has two chromosomes (shown here in yellow and blue in the leftmost cell) before meiosis starts. These chromosomes are replicated to produce sister chromatids that are held together by cohesins (grey circles around the sister chromatids). During the next stage of meiosis, called Prophase I, chromosomes with similar sequences form pairs and undergo recombination, creating physical links that hold the homologs together. Next, during metaphase I, the sister kinetochores (black circles) are clamped together by a protein complex called monopolin, and the spindle microtubules (purple) attach homologous chromosomes to spindle poles (also purple) at opposite ends of the cell. Homologous chromosomes then segregate during anaphase I. During metaphase II, sister chromatids attach to opposite spindle poles and separate in anaphase II, creating meiotic products with half the set of chromosomes.
During the first round of segregation, called meiosis I, spindle microtubules attach themselves to the chromosomes with the help of large protein complexes called kinetochores that are found on each chromatid (see Figure 1). In addition to attaching the microtubules to the chromosomes, the kinetochores also correct improper attachments and move the chromosomes along microtubules. In meiosis I, the paired chromosomes segregate to opposite ends (or poles) of the spindle. In meiosis II essentially the same cast of players (that is, spindle microtubules and kinetochores), segregate the sister chromatids to produce a total of four cells. The MIT-UCSF team used budding yeast as a model to study these processes and interactions in greater detail.
Three mechanisms help ensure the proper attachment of chromosomes to spindle microtubules in meiosis I. First, during prophase, which is the first stage of meiosis I, pairs of homologous chromosomes undergo recombination. This process creates physical links that hold the homologs together, and ensures their attachment to opposite spindle poles (Brar and Amon, 2008). Second, the sister kinetochores offer only one site for microtubules to bind to: in budding yeast, for example, a protein complex called monopolin clamps the sister kinetochores together just before microtubule attachment begins. Third, protein rings made up of cohesins are thought to encircle the two sister chromatids: this creates cohesion between the chromatids and prevents them from separating prematurely during meiosis I. When the two homologous chromosomes are attached to opposite spindle poles during metaphase I (a stage after prophase), the spindle forces are resisted by the physical linkages and the cohesion between sister chromatids. Together these three mechanisms ensure that homologous chromosomes are segregated in meiosis I, while sister chromatids remain together.
The work of Miller and Ünal, who are joint first authors on the paper, and their co-workers reveals another level of regulation of meiosis I that involves proteins called M phase cyclins. When the enzyme cyclin-dependent kinase (Cdk) is bound to a cyclin, it drives cell cycle events by phosphorylating substrates (Enserink and Kolodner, 2010). Two of the cyclins that have a role in driving the cells through meiosis, Clb1 and Clb3, are transcribed at the end of prophase (Dahmann and Futcher, 1995 Chu et al., 1998 Carlile and Amon, 2008). However, if either of these cyclins is expressed prematurely, the spindle microtubules are assembled too early and, as a result, sister chromatids are segregated rather than chromosomes in a significant fraction (∼40%) of the cells (see Figure 2). This is surprising because Cdk-Clb1 is normally present (and active) during meiosis I.
Proper timing of the interactions between spindle microtubules and kinetochores is essential for meiosis to proceed correctly. During metaphase I in normal meiosis (top), homologous chromosomes become attached to opposite spindle poles by spindle microtubules, and are then segregated in anaphase I (as shown in Figure 1). However, if the microtubules attach to the kinetochores prematurely (bottom), sister chromatids will be segregated in meiosis I, which can ultimately lead to miscarriage or birth defects in babies.
Previously Amon and co-workers have shown that the presence of the monopolin complex during mitosis (as opposed to meiosis) can clamp sister kinetochores together and lead to a meiosis I chromosome segregation pattern (Monje-Casas et al., 2007). Miller et al. now propose that for the monopolin complex to clamp sister kinetochores together, it must associate with them before they attach to microtubules. In the cells in which Clb1 or Clb3 are prematurely expressed, microtubules attach to both sister kinetochores before monopolin is active, and this leads to the segregation of sister chromatids. However, if attachment begins after monopolin becomes active, it is the chromosomes that are segregated.
To test this model, the MIT-UCSF team arrested cells undergoing mitosis after the microtubules had attached to the sister kinetochores and then induced monopolin: the sister kinetochores remained attached to the microtubules and segregated to opposite spindle poles when the cell was released from the arrest. However, if the drug nocodazole was used to depolymerize the microtubules during the arrest period, monopolin was able to clamp sister kinetochores together and almost half (48%) of sister chromatids moved to the same spindle pole. Furthermore, if the microtubules in cells that prematurely expressed Clb3 were depolymerized, the meiosis I chromosome segregation pattern was rescued. These experiments suggest that the timing of the attachment of chromosomes to microtubules is carefully regulated in meiosis to prevent premature kinetochore–microtubule interactions. And other experiments suggest that cells prevent premature interactions of kinetochores and microtubules by dismantling the outer regions of the kinetochore. Taken together all these results suggest that Miller et al have uncovered two additional mechanisms that cells use to ensure the segregation of chromosomes in meiosis I: restricting the activity of cyclin-dependent kinase bound to M phase cyclins in prophase, and also restricting the assembly of the kinetochore in prophase.
Miller, Ünal and co-workers have demonstrated that premature kinetochore–microtubule interactions lead to a mitotic pattern of chromosome segregation in meiosis I. Since this can lead to gametes with missing or extra chromosomes, which can cause miscarriage and birth defects in babies, it is crucial that we continue to improve our understanding of meiosis (Nagaoka et al., 2012). By revealing a number of hitherto unknown mechanisms used by cells to regulate the meiotic cell cycle, this work represents an important step in this quest.
What Are Sister Chromatids?
As mentioned above, sister chromatids are identical copies of a chromosome that has been unfurled and replicated, then bound to its partner with a centromere. During the interphase portion of the cell cycle&mdashthe time between replications&mdashall of the chromosomes are duplicated in preparation for cell division. When these sister chromatids eventually separate, it is to ensure that both daughter cells end up with the correct number of chromosomes. That being said, while sister chromatids are present in both mitosis and meiosis, their behavior during these two cellular activities.
Sister Chromatids in Meiosis
Since sex cell replication (meiosis) is slightly different than your average cell division, the replication process is slightly different, as is the movement of sister chromatids. There are homologous chromosomes of duplicated sister chromatids in the first step of meiosis, and these homologous chromosomes separate and move to their individual daughter cells during anaphase 1, then separate during telophase I. However, in anaphase II, the sister chromatids are pulled apart by the spindle towards opposite centrosomes. Thus, the result of meiosis is four daughter cells with half the number of chromosomes (23), which is the desired amount for a sex cell.
Stage of Meiosis (Photo Credit : Ali Zifan / Wikimedia Commons)
Interestingly enough, the sister chromatids are also involved in one of the more important stages of meiosis&mdashgenetic recombination. It is during this crossing over and swapping of DNA chunks between homologous chromosomes and sister chromatids that so much of the variety and diversity of our genetic expression comes from.
Sister Chromatids in Mitosis
In mitosis&mdashthe cellular replication and division of a somatic cell&mdashthe chromosomes replicate into sister chromatids before prophase begins, at which point they migrate to the center of the cell. During anaphase, the spindles pull the sister chromatids apart and tug them towards opposing centrosomes. During telophase, the original cell divides into two daughter cells, each of which has a full set of 46 chromosomes, which are known as daughter chromosomes.
Mammalian STAG3 is a cohesin specific to sister chromatid arms in meiosis I
Cohesins, which have been characterized in budding yeast 1,2 and Xenopus 3 , are multisubunit protein complexes involved in sister chromatid cohesion. Regulation of the interactions among different cohesin subunits and the assembly/disassembly of the cohesin complex to chromatin are key steps in chromosome segregation. We previously characterized the mammalian STAG3 protein as a component of the synaptonemal complex that is specifically expressed in germinal cells 4 , although its function in meiosis remains unknown. Here we show that STAG3 has a role in sister chromatid arm cohesion during mammalian meiosis I. Immunofluorescence results in prophase I cells suggest that STAG3 is a component of the axial/lateral element of the synaptonemal complex. In metaphase I, STAG3 is located at the interchromatid domain and is absent from the chiasma region. In late anaphase I and the later stages of meiosis, STAG3 is not detected. STAG3 interacts with the structural maintenance chromosome proteins SMC1 and SMC3, which have been reported to be subunits of the mitotic cohesin complex 2,3 . We propose that STAG3 is a sister chromatid arm cohesin that is specific to mammalian meiosis I.