Multiple two-polymerase mechanisms in mammalian translesion DNA synthesis
Multiple two-polymerase mechanisms in mammalian translesion DNA synthesis
复制标题
DOI：
10.4161/cc.9.4.10727
复制
发表时间：
2010-02-15
期刊：
影响因子：
4.3
通讯作者：
Shachar, Sigal
中科院分区：
文献类型：
--
作者：
Livneh, Zvi;Ziv, Omer;Shachar, Sigal
复制叉子与DNA损伤的接触可能导致叉子停滞和/或形成单链间隙。处理这些复制异常的一个主要策略是跨病变DNA合成(TLS)，在这种合成中，专门的容易出错的DNA聚合酶绕过阻断病变。最近的研究表明，跨越特定DNA损伤的TLS可能涉及多达四种不同的TLS聚合酶，它们作用于两个聚合酶反应，其中特定聚合酶插入后，另一个聚合酶延伸。插入决定了TLS反应的准确性和突变特异性，并由PolETA、Polkappa或Poliota等几种聚合酶中的一种进行。相比之下，延期主要由Poll Zeta执行。在XPV患者的细胞中，由于PolETA的缺陷，跨环丁烷嘧啶二聚体(CPD)的TLS缺乏，TLS由至少两个备份反应进行，每个反应涉及两个聚合酶：一个反应涉及Polkappa和polZeta，另一个反应涉及poliota和polZeta。这些机制也可能在过量紫外线损伤下帮助正常细胞中的PolETA。
The encounter of replication forks with DNA lesions may lead to fork arrest and/or the formation of single-stranded gaps. A major strategy to cope with these replication irregularities is translesion DNA synthesis (TLS), in which specialized error-prone DNA polymerases bypass the blocking lesions. Recent studies suggest that TLS across a particular DNA lesion may involve as many as four different TLS polymerases, acting in two-polymerase reactions in which insertion by a particular polymerase is followed by extension by another polymerase. Insertion determines the accuracy and mutagenic specificity of the TLS reaction, and is carried out by one of several polymerases such as pol eta, pol kappa or pol iota. In contrast, extension is carried out primarily by pol zeta. In cells from XPV patients, which are deficient in TLS across cyclobutane pyrimidine dimers (CPD) due to a deficiency in pol eta, TLS is carried out by at least two backup reactions each involving two polymerases: One reaction involves pol kappa and pol zeta, and the other pol iota and pol zeta. These mechanisms may also assist pol eta in normal cells under an excessive amount of UV lesions.