Translesion DNA synthesis in the context of cancer research.

Translesion DNA synthesis in the context of cancer research.
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DOI:
10.1186/1475-2867-11-39
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发表时间:
2011-11-02
影响因子:
5.8
通讯作者:
Marti TM
Marti TM
中科院分区:
医学2区
文献类型:
--
作者:
Knobel PA;Marti TM

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在细胞分裂过程中,基因组DNA的复制是由高保真DNA聚合酶进行的,但这些无错误的酶不能合成受损的DNA。专门的DNA聚合酶,所谓的DNA translesion synthesis polymerases(TLS polymerases),可以复制受损的DNA,从而避免复制叉断裂和随后的染色体不稳定性。我们专注于哺乳动物TLS聚合酶参与DNA损伤耐受机制。详细地,我们回顾了TLS聚合酶的发现,并描述了所有哺乳动物的TLS聚合酶的分子特征。我们简要概述了调节TLS聚合酶的选择性和活性的机制。此外,我们总结了目前的知识如何不同类型的DNA损伤,相关的诱导或治疗癌症,绕过TLS聚合酶。最后,我们阐明了TLS聚合酶在癌症治疗中的相关性。
During cell division, replication of the genomic DNA is performed by high-fidelity DNA polymerases but these error-free enzymes can not synthesize across damaged DNA. Specialized DNA polymerases, so called DNA translesion synthesis polymerases (TLS polymerases), can replicate damaged DNA thereby avoiding replication fork breakdown and subsequent chromosomal instability. We focus on the involvement of mammalian TLS polymerases in DNA damage tolerance mechanisms. In detail, we review the discovery of TLS polymerases and describe the molecular features of all the mammalian TLS polymerases identified so far. We give a short overview of the mechanisms that regulate the selectivity and activity of TLS polymerases. In addition, we summarize the current knowledge how different types of DNA damage, relevant either for the induction or treatment of cancer, are bypassed by TLS polymerases. Finally, we elucidate the relevance of TLS polymerases in the context of cancer therapy.
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