Regulation of sister chromatid cohesion during the mitotic cell cycle

Abstract

Orderly execution of two critical events during the cell cycle--DNA replication and chromosome segregation--ensures the stable transmission of genetic materials. The cohesin complex physically connects sister chromatids during DNA replication in a process termed sister chromatid cohesion. Timely establishment and dissolution of sister chromatid cohesion is a prerequisite for accurate chromosome segregation, and is tight regulated by the cell cycle machinery and cohesin-associated proteins. In this review, we discuss recent progress in the molecular understanding of sister chromatid cohesion during the mitotic cell cycle.cell cycle, mitosis, sister chromatid cohesion, cohesin, cohesin loading, cohesin release, DNA replication, cohesion establishment Citation:Zheng G, Yu HT. Regulation of sister chromatid cohesion during the mitotic cell cycle. Sci China Life Sci, 2015Sci, , 58: 1089Sci, -1098Sci, , doi: 10.1007 During the cell cycle, DNA undergoes replication during S phase to generate two identical copies of each chromosome, called sister chromatids. During mitosis, sister chromatids are separated and partitioned evenly to the two daughter cells to maintain genomic stability. Cells receive too many or too few chromosomes become aneuploid. Aneuploidy can drive tumorigenesis in a context-dependent manner [1,2]. To prevent premature sister chromatid separation and ensure accurate chromosome segregation, sister chromatids are physically tethered to each other through the process of sister chromatid cohesion, as well as DNA catenation, from S phase till metaphase. Sister chromatid cohesion is mediated by the highly conserved ring-shaped cohesin complex, which topologically entraps chromosomes [3,4]. Cohesion establishment, maintenance, and removal at different cell cycle phases require a series of coordinated interactions between cohesin and its regulators (Figure 1). Cohesin is loaded onto DNA by the cohesin loader complex Scc2-Scc4 in telophase and early G1 [57]. At this stage, the chromatin-bound cohesin is highly dynamic, and can be released from chromosomes by the cohesin releasing factor Wapl, with the help of the scaffold protein Pds5 [811]. During S phase, the replicated sister chromatids are tethered by cohesin to establish sister chromatid cohesion. Cohesion establishment requires the acetylation of two adjacent, evolutionarily conserved lysines on Smc3 by the acetyltransferase Eco1 (Esco1/2 in vertebrates) [1217], and in metazoans, the subsequent recruitment of sororin to cohesin through Pds5 [1821]. Smc3 acetylation and sororin antagonize the cohesin-releasing activity of Wapl-Pds5, thereby stabilizing cohesin on chromosomes [17,21]. Finally, in mitosis, cohesin is released from chromosomes in a stepwise manner in vertebrates [22]. In early mitosis, Pds5-bound sororin is phosphorylated by mitotic kinases and dissociates from cohesin [21,2325]. Sororin dissociation allows Wapl to gain access to Pds5 and cohesin, releasing cohesin from chromosome arms. At centromeres,

Polo-like kinase 1 (PLK1)-dependent phosphorylation of methylenetetrahydrofolate reductase (MTHFR) regulates replication via histone methylation

“…40 And recently it was shown that overexpression of SUV4-20H2 rescued the cohesin and H4K20me3 defects of Rb-depleted cells. 41 Since replication defects could very well lead to cohesin defects, 42 our data suggest that cohesin phenotypes in Rbdevoid cells might be secondary to replication.…”

Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

“…Alterations of TP53 are predictive for BUC recurrence and are markedly associated with an unfavorable prognosis after radical cystectomy 28,29. GO enrichment analysis for biological processes demonstrated that BUC tumors were associated with mitotic recombination, sister chromatid segregation, and mitotic sister chromatid segregation, all of which are related to cell cycle regulation 30–32. Our results, moreover, are supported by the study of Guo et al,33 which identified that genes involved in sister chromatid segregation were frequently altered in bladder cancer via whole-genome and whole-exome sequencing.…”

Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy

“…During interphase, cohesin mediates the formation of chromosome loops that impact transcription (11). During S phase, cohesin physically links replicated chromosomes to establish sister-chromatid cohesion (12,13), which is a prerequisite for faithful chromosome segregation during mitosis. Finally, cohesin contributes to homologydirected repair of DNA breaks, in part, through holding the sister chromatid in proximity of the breaks and presenting it as the repair template (14).…”