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Importance of Polη for damage-induced cohesion reveals differential regulation of cohesion establishment at the break site and genome-wide

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干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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Correct chromosome segregation requires that sister chromatids are held together by the protein complex cohesin, from S phase until anaphase. This S phase established cohesion is, together with DSB recruitment of cohesin and formation of damage induced (DI) cohesion, also important for repair of DSBs. Eco1 is a common essential factor for S phase and DI-cohesion. The fission yeast Eco1ortholog, Eso1, is important both for S phase cohesion and for bypass of UV induced lesions, and is expressed as a fusion protein with Polη. The cohesion function has been attributed solely to Eso1 and the lesion bypass function to the Polη part of the protein. As we found the interaction between the two proteins intriguing we decided to look for a functional connection also in budding yeast. Indeed, despite being dispensable for S phase cohesion, budding yeast Polη is required for formation of DI genome-wide cohesion. However, Polη deficient cells are 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.
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2022-02-20
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