DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity.
DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity.
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DOI：
10.1093/nar/gkr596
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发表时间：
2012-01
影响因子：
14.9
通讯作者：
Livneh Z
中科院分区：
文献类型：
--
作者：
Diamant N;Hendel A;Vered I;Carell T;Reissner T;de Wind N;Geacinov N;Livneh Z
翻译DNA合成（TLS）使用低保真DNA聚合酶绕过复制阻断病变，并且被认为与染色体复制相关，发生在细胞周期的S期。利用抗复制蛋白A抗体的免疫染色，我们发现在紫外线照射的哺乳动物细胞中，在复制过程中S期形成的染色体单链间隙持续到细胞周期的G2期，在此阶段它们的修复依赖于DNA聚合酶ζ和Rev1完成。利用高分辨率间隙质粒分析系统对特定细胞周期期离心洗脱富集的细胞群体进行TLS分析，结果表明TLS在S和G2中都起作用。此外，TLS在G2中的诱变特异性与S不同，在某些情况下总体突变频率更高。这些结果表明，DNA损伤引起的单链间隙的TLS修复可能滞后于染色体复制，可与染色体复制分离，并且发生在细胞周期的S期和G2期。这种机制可以维持有效的复制，尽管存在DNA损伤，TLS滞后并修补不连续区域，但复制仍可以进行。
Translesion DNA synthesis (TLS) employs low-fidelity DNA polymerases to bypass replication-blocking lesions, and being associated with chromosomal replication was presumed to occur in the S phase of the cell cycle. Using immunostaining with anti-replication protein A antibodies, we show that in UV-irradiated mammalian cells, chromosomal single-stranded gaps formed in S phase during replication persist into the G2 phase of the cell cycle, where their repair is completed depending on DNA polymerase ζ and Rev1. Analysis of TLS using a high-resolution gapped-plasmid assay system in cell populations enriched by centrifugal elutriation for specific cell cycle phases showed that TLS operates both in S and G2. Moreover, the mutagenic specificity of TLS in G2 was different from S, and in some cases overall mutation frequency was higher. These results suggest that TLS repair of single-stranded gaps caused by DNA lesions can lag behind chromosomal replication, is separable from it, and occurs both in the S and G2 phases of the cell cycle. Such a mechanism may function to maintain efficient replication, which can progress despite the presence of DNA lesions, with TLS lagging behind and patching regions of discontinuity.
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影响因子：
16
作者：
Berdichevsky, A;Izhar, L;Livneh, Z
通讯作者：
Livneh, Z
影响因子：
21.3
作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.3
作者：
Lang GI;Murray AW
通讯作者：
Murray AW
影响因子：
14.9
作者：
Gentil, A;LePage, F;Sarasin, A
通讯作者：
Sarasin, A