Abstract
Genome integrity depends on correct chromosome segregation, which in turn relies on cohesion between sister chromatids from S phase until anaphase. S phase cohesion, together with DNA double-strand break (DSB) recruitment of cohesin and formation of damage-induced (DI) cohesion, has previously been shown to be required also for efficient postreplicative DSB repair. The budding yeast acetyltransferase Eco1 (Ctf7) is a common essential factor for S phase and DI-cohesion. The fission yeast Eco1 ortholog, Eso1, is expressed as a fusion protein with the translesion synthesis (TLS) polymerase Polη. The involvement of Eso1 in S phase cohesion was attributed to the Eco1 homologous part of the protein and bypass of UV-induced DNA lesions to the Polη part. Here we describe an additional novel function for budding yeast Polη, i.e. formation of postreplicative DI genome-wide cohesion. This is a unique Polη function not shared with other TLS polymerases. However, Polη deficient cells are DSB repair competent, as Polη is not required for cohesion locally at the DSB. This reveals differential regulation of DSB–proximal cohesion and DI genome-wide cohesion, and challenges the importance of the latter for DSB repair. Intriguingly, we found that specific inactivation of DI genome-wide cohesion increases chromosomal mis-segregation at the entrance of the next cell cycle, suggesting that S phase cohesion is not sufficient for correct chromosome segregation in the presence of DNA damage.
Highlights
Correct chromosome segregation is fundamental for genome integrity, and facilitated by the cohesin complex, that tethers sister chromatids from S phase until anaphase, a function known as cohesion [1,2,3]
Correct chromosome segregation requires that sister chromatids are held together by the protein complex cohesin, from S phase until anaphase
Polgdeficient cells are double-strand break (DSB) repair competent, revealing differential regulation of DI-cohesion at the break and genome-wide. This finding challenges the importance of DI genome-wide cohesion for DSB repair, and based on our findings we suggest that S phase cohesion is not sufficient for correct chromosome segregation in the presence of DNA damage
Summary
Correct chromosome segregation is fundamental for genome integrity, and facilitated by the cohesin complex, that tethers sister chromatids from S phase until anaphase, a function known as cohesion [1,2,3]. Cohesion is established during S phase in an incompletely understood process that is closely connected with replication and depends on acetylation of Smc by the highly conserved acetyltransferase Eco ( called Ctf7) [10,11,12]. Several proteins have been shown to be important for cohesion establishment, including Ctf, a subunit of an alternative replication factor C (RFC) complex and the proliferating cell nuclear antigen (PCNA), [13,14,15,16]. Cohesion is maintained until anaphase, when it is dissolved through cleavage of Scc by the enzyme separase (for a review see [3])
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