Loading of cohesin and cohesion generation in response to DNA damage.

Abstract

The sister chromatids are held together by the conserved cohesin complex from DNA replication in S phase until the metaphase to anaphase transition during mitosis. Generation of sister chromatid cohesion is essential for creating bipolar attachments between chromosomes and microtubules to allow equal segregation of sister chromatids in anaphase. In addition, the cohesin complex plays important roles in DNA damage checkpoint signaling and repair of DNA double strand breaks. In mammalian and yeast studies it was shown that the cohesin complex and its important loading factors are recruited to sites of DNA damage. Recent yeast studies indicate that not only local cohesion is generated at the damaged site. Remarkably, DNA damage triggers genome-wide cohesion establishment. However, it is still unknown if this is similar in mammalian cells. Phosphorylation of the cohesin complex components, SMC1 and SMC3, plays important roles in DNA damage induced checkpoint signalling in human cells. Several post-translational modifications mediate the different functions of the cohesin complex. Here, the role of the cohesin complex during DNA damage and its post-translational modifications are discussed, with a specific focus on the differences between yeast and human.