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Regulation of the abundance of Y-family polymerases in the cell cycle of budding yeast in response to DNA damage.
Current Genetics ( IF 2.5 ) Pub Date : 2020-02-19 , DOI: 10.1007/s00294-020-01061-3
Aleksandra Sobolewska 1 , Agnieszka Halas 1 , Michal Plachta 1 , Justyna McIntyre 1 , Ewa Sledziewska-Gojska 1
Affiliation  

Y-family DNA polymerases mediate DNA damage tolerance via translesion synthesis (TLS). Because of the intrinsically error-prone nature of these enzymes, their activities are regulated at several levels. Here, we demonstrate the common regulation of the cellular abundance of Y-family polymerases, polymerase eta (Pol eta), and Rev1, in response to DNA damage at various stages of the cell cycle. UV radiation influenced polymerase abundance more when cells were exposed in S-phase than in G1- or G2-phases. We noticed two opposing effects of UV radiation in S-phase. On one hand, exposure to increasing doses of UV radiation at the beginning of this phase increasingly delayed S-phase progression. As a result, the accumulation of Pol eta and Rev1, which in nonirradiated yeast is initiated at the S/G2-phase boundary, was gradually shifted into the prolonged S-phase. On the other hand, the extent of polymerase accumulation was inversely proportional to the dose of irradiation, such that the accumulation was significantly lower after exposure to 80 J/m2 in S-phase than after exposure to 50 J/m2 or 10 J/m2. The limitation of polymerase accumulation in S-phase-arrested cells in response to high UV dose was suppressed upon RAD9 (but not MRC1) deletion. Additionally, hydroxyurea, which activates mainly the Mrc1-dependent checkpoint, did not limit Pol eta or Rev1 accumulation in S-phase-arrested cells. The results show that the accumulation of Y-family TLS polymerases is limited in S-phase-arrested cells due to high levels of DNA damage and suggest a role of the Rad9 checkpoint protein in this process.



中文翻译:

响应DNA损伤,在发芽酵母的细胞周期中调控Y家族聚合酶的丰度。

Y家族DNA聚合酶通过跨病变合成(TLS)介导DNA损伤耐受性。由于这些酶的内在易错性,它们的活性被调节在几个水平上。在这里,我们展示了Y家族聚合酶,聚合酶eta(Pol eta)和Rev1在细胞周期各个阶段对DNA损伤的响应,它们对细胞丰度的共同调节。当细胞暴露于S相时,紫外线辐射对聚合酶丰度的影响大于G1或G2相。我们注意到在S相中UV辐射有两个相反的影响。一方面,在此阶段开始时暴露于不断增加的紫外线辐射剂量会越来越延迟S期进程。结果,未辐照酵母中的Pol eta和Rev1积累在S / G2相边界开始,逐渐过渡到延长的S期。另一方面,聚合酶积累的程度与辐照剂量成反比,因此暴露于80 J / m后积累明显降低2在S相比暴露于50焦耳后/米2或10焦耳/米2RAD9(但不是MRC1)的缺失抑制了高剂量紫外线引起的S期阻滞细胞聚合酶积累的限制。此外,主要激活Mrc1依赖性检查点的羟基脲并没有限制S期阻滞细胞的Pol eta或Rev1积累。结果表明,由于高水平的DNA损伤,Y族TLS聚合酶在S期停滞细胞中的积累受到限制,并提示Rad9检查点蛋白在此过程中的作用。

更新日期:2020-02-19
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