INDIVIDUAL PROJECT: COHESION REC8 PROTEIN
Meiosis cell division is preceded by the duplication of homologous chromosomes, resulting in 2 sister chromatids, which are the replicated copies of the original chromosome. These sister chromatids are being held together through their centromeres and such cohesion is important to assist both of them to move together to the same spindle pole and be able to bind to microtubules before segregating way from each other during the second meiotic division, each going into a different cell. “Maintenance of the association of the sister chromatids until the onset of nuclear division is essential for faithful partitioning of the genetic material between the future daughter cells”. (Amon, 1999)
Regulation of sister-chromatids cohesion during meiosis
At metaphase I, sister-chromatid pairs from homologous chromosomes are held together by chiasmata, and are stabilized by meiosis-specific cohesin complexes present on chromosomal arms distal to the chiasma. Then at the onset of anaphase I, protein Esp1 cleaves the cohesin complex, which contains protein Rec8, allowing sister-chromatid separation.
In meiosis, cohesion along the chromosome arm is lost during meiosis I to release recombined homologue connections, whereas centromeric cohesion is maintained until meiosis II.(Watanabe,1999)
During Meiosis, cohesin Rec8 is required for the sister-chromatids to remain associated for reductional segregation in the first meiotic cell division, thus assisting both sister-chromatids to move together to the same pole. During the pre-meiotic phase, Rec8 appearsin the centromeres and adjacent chromosome arms, and centromeric Rec8 persissts throughout meiosis I until anaphase of meiosis II that it disappears. (Watanabe, 1999) As Rec8 disappear, sister chromatid can hence separate, resulting in equational segregation.
Function and localization of Rec8
The cohesion is made possible by a meiosis-specific cohesion protein, which is known as “Cohesin Rec8”. It “replaces the SCC1 mitosis-specific cohesin to ensure sister chromatid cohesion during meiosis.” (Yamamoto, 2003)
It “lines the entire longitudinal axes of pachytene chromosomes” (Buonomo, 2000), at the centromere and along the chromosomal arms, and is “cleaved by ESP1 shortly before the first meiotic division,” (Yamamoto, 2003) which dissociates Rec8 from chromosome arms, but it “persists in the vicinity of centromeres until the onset of anaphase II” (Buonomo, 2000), thus initiating the segregation of sister chromatids.
Although the localization pattern of Rec8 in budding yeast and fission yeast is different, with Rec8 present along the entire length of the chromosome in Saccharomyces cerevisiae; and is present only around centromeres and adjacent chromosomal arms of Schizosaccharomyces pombe. “In both yeasts, Rec8 is lost along chromosomal arms at the onset of anaphase I but persists at the centromeric regions. Centromeric Rec8 staining then disappears during meiosis II.” (Amon, 1999)
Experiments on mutants lacking protein Rec8
The importance of Rec8 in sister-chromatid cohesion and its maintenance at centromeric regions beyond metaphase I is shown via experiments on mutants that lack the protein Rec8.
- Mutants without protein Rec8 undergo pre-cocious sister-chromatid separation during meiosis I.
- Protein Rec8 is also important for reductional chromosome segregation at meiosis division.
- It is shown that mutant fission yeast S. pombe lack of Rec8 “results in a shift of the segregation pattern from reductional to equational during the first meiotic division” (Amon, 1999). Therefore it is proven that a reductional segregation requires the presence of protein Rec8 at centromeres during meiosis I for the sister chromatids to remain associated and move together towards the same spindle pole, and that this is necessary for the reduction of diploid zygote to haploid gametes. (Watanabe, 1999)
- Protein Rec8 is also important for recombination during meiosis.
- It is shown that there is a reduction in recombination around centromeres in S. pombe rec8− mutants; and that in S. cerevisiae rec8− mutants, there is a reduced ability to repair double-stranded breaks, indicating that cohesion is critical for the location of these homologous targets for the repair of these breaks.
Cleavage of Rec8
The initiation of sister-chromatid segregation takes place at the onset of anaphase II as protein Rec8 is being cleaved by a specialized endopeptidase called separin. Experimental results from noncleavable mutation in Rec8’s potential separin cleavage sites show that such mutation prevents the disappearance of Rec8 from chromosome arms during the first meiotic division, which in turn blocks homolog disjunction. This shows that the cleavage of protein Rec8 requires the resolution of chiasmata, hence the disjunction of homologs. It has also been suggested that Rec8 in the vicinity of centromeres maybe protected from separin throughout the first meiotic division, yet such mechanism is still unknown.
In conclusion, the meiosis-specific cohesion protein Rec8 is critical for the association of the sister chromatids produced by chromosomal duplication through their centromeres, and is lost in a stepwise manner that correlates with the loss of sister-chromatid cohesion, thus initiating sister-chromatid segregation.
Research have been carried out by scientists and experiments have been done on Rec8. Although Rec8 is a meiosis specific cohesion protein, it has been used to experimentally expressed during mitosis cell division. However, although it still attaches the two sister chromatids together, it is also destroyed along the arms and centromeres at the same time, which shows that the behaviour of Rec8 during meiosis does not depend on the protein's intrinsic matters. Instead, scientists hypothesized that there must be another protein expressed specifically during meiosis to protect Rec8 from being destroyed, and they found out about a previously unknown protein, which they have named Sgo1. Further research on this new protein is needed to understand more about the mechanisms of Rec8.
1. Amon, A (1999).Meiosis: Rec8 is the reason for cohesion. Nature Cell Biology. 1, 125-127.
2. Buonomo, Sara B. C. (2000).Disjunction of Homologous Chromosomes in Meiosis I Depends on Proteolytic Cleavage of the Meiotic Cohesin Rec8 by Separin. Developmental Cell. 103, 387-398.
3. Watanabe, Y (1999).Cohesin Rec8 is required for reductional chromosome segregation at Meiosis.. Nature. 400, 6743.
4. Yamamoto, A (2003).Linear element formation and their role in meiotic sister chromatid cohesion and chromosome pairing.. Journal of Cell Science. 116, 1719-1731.