DNA damage tolerance: when it's OK to make mistakes.

DNA damage tolerance: when it's OK to make mistakes.
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DOI:
10.1038/nchembio.139
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发表时间:
2009-02
影响因子:
14.8
通讯作者:
Cimprich, Karlene A.
Cimprich, Karlene A.
中科院分区:
生物学1区
文献类型:
--
作者:
Chang, Debbie J.;Cimprich, Karlene A.

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在遗传多样性有利的条件下,突变可能是有益的,例如体细胞超突变和抗体产生,但当它们破坏基本的细胞过程或导致不受控制的增殖和癌症时,它们也可能是致命的。突变是由内源性和外源性DNA损伤剂产生的损伤的不准确加工引起的,并且基因组在S期期间特别容易受到这种损伤。在细胞周期的这一阶段,DNA模板中的许多损伤会阻止复制。为了保持叉的稳定性和确保DNA复制的完成,必须绕过这些损伤。病变绕过是通过一组易错和无错的过程进行的,这些过程统称为DNA损伤耐受机制。在这里,我们讨论了两种类型的DNA损伤耐受性,translesion合成和模板转换,在停滞的复制叉由PCNA的泛素化,以及它们发生的条件下进行调节。
Mutations can be beneficial under conditions where genetic diversity is advantageous, such as somatic hypermutation and antibody generation, but they can also be lethal when they disrupt basic cellular processes or cause uncontrolled proliferation and cancer. Mutations arise from inaccurate processing of lesions generated by endogenous and exogenous DNA damaging agents, and the genome is particularly vulnerable to such damage during S phase. In this phase of the cell cycle, many lesions in the DNA template block replication. Such lesions must be bypassed in order to preserve fork stability and to ensure completion of DNA replication. Lesion bypass is carried out by a set of error-prone and error-free processes collectively referred to as DNA damage tolerance mechanisms. Here, we discuss how two types of DNA damage tolerance, translesion synthesis and template switching, are regulated at stalled replication forks by ubiquitination of PCNA, and the conditions under which they occur.
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