Cohesin
Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping.
The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring.
Cohesin was separately discovered in budding yeast (Saccharomyces cerevisiae) both by Douglas Koshland[1] and Kim Nasmyth in 1997.
This includes a binding site for SA1 or SA2,[5] recognition motifs for separase cleavage[6] and a region that is competitively bound by PDS5A, PDS5B or NIPBL.
[13] Although these two functions are tightly interlinked, it has been possible to separate them by creating a cohesin hinge mutant that can extrude loops but cannot maintain cohesion.
It participates in repairing double-strand breaks in DNA via homologous recombination, where the sister chromatid is used as a template for sequence reconstruction.
[22] Cohesin might play an important role in regulation of gene expression through the following mechanisms: Cohesin binding along the chromosomal DNA is considered to be dynamic and its location changes based on gene transcription, specific DNA sequence and presence of chromosome-associated proteins.
[11] In addition, disturbing the ring structure of cohesin through cleavage of Smc3 or Scc1 triggers premature sister chromatid segregation in vivo.
[44] Dissociation of sister chromatids cohesion defines anaphase onset, which establishes two sets of identical chromosomes at each pole of the cell (telophase).
To avoid premature sister chromatid separation, the APC/C is maintained in an inactive state bound to different molecules, which are part of a complex mechanism termed the spindle assembly checkpoint.
Cohesin proteins SMC1β, SMC3, REC8 and STAG3 appear to participate in cohesion of sister chromatids throughout the meiotic process in human oocytes.
A homozygous frameshift mutation in the Stag3 gene was identified in a large consanguineous family with premature ovarian failure.
During meiosis, establishment of cohesion of sister chromatids via cohesin rings is necessary for ensuring homologous recombination-mediated DNA repair and subsequent proper chromosome segregation.
[48] Also, variants of cohesin proteins are associated with primary ovarian insufficiency, trisomy in offspring and non-obstructive azoospermia.
[48] Oocyte loss is a natural process that accelerates as women enter their mid-thirties, and thus has a significant effect on female reproduction.
[75] The cohesin subunit STAG2 appears to play a significant role in hematopoietic function, as its loss enhances stem cell self-renewal while impairing differentiation.
