Sister chromatid cohesion

Abstract

During S phase, not only does DNA have to be replicated, but also newly synthesized DNA molecules have to be connected with each other. This sister chromatid cohesion is essential for the biorientation of chromosomes on the mitotic or meiotic spindle, and is thus an essential prerequisite for chromosome segregation. Cohesion is mediated by cohesin complexes that are thought to embrace sister chromatids as large rings. Cohesin binds to DNA dynamically before DNA replication and is converted into a stably DNA-bound form during replication. This conversion requires acetylation of cohesin, which in vertebrates leads to recruitment of sororin. Sororin antagonizes Wapl, a protein that is able to release cohesin from DNA, presumably by opening the cohesin ring. Inhibition of Wapl by sororin therefore "locks" cohesin rings on DNA and allows them to maintain cohesion for long periods of time in mammalian oocytes, possibly for months or even years.

Figure 1.

The cohesin complex. A schematic illustration of how cohesin subunits might be arranged in vertebrate cohesin complexes that mediate sister chromatid cohesion by embracing the two sister chromatid strands.

Figure 2.

The cohesin cycle in vertebrate cells. A schematic illustration showing cohesin loading, cohesion establishment, and cohesin removal from chromosomes in telophase/G₁ phase, S phase, and mitosis, respectively. (Small circles) Cohesin complexes; (light gray circles) cohesin complexes that are dynamically bound to DNA; (dark gray circles) “cohesive” complexes that are stably bound to DNA (Gerlich et al. 2006).

Figure 3.

Dynamic and stable binding modes of cohesin to DNA. A schematic drawing illustrating how adherin-mediated separation of the hinge domains of Smc1 and Smc3 might create an entry gate for DNA into the cohesin ring, whereas a transient Wapl-mediated dissociation of Scc1 from the SMC subunits may release cohesin from DNA by generating an exit gate (Nasmyth 2011; Chan et al. 2012). Wapl’s ability to open this exit gate might be inhibited by sororin, which binds to cohesin in vertebrates following Smc3 acetylation and possibly other unidentified events during DNA replication (Nishiyama et al. 2010).