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叉状DNA模板支持绕过在单链模板上阻断DNA合成的损伤进行复制。

Fork-like DNA templates support bypass replication of lesions that block DNA synthesis on single-stranded templates.

作者信息

Hoffmann J S, Pillaire M J, Lesca C, Burnouf D, Fuchs R P, Defais M, Villani G

机构信息

Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Unité Propre de Recherche 9062, Toulouse, France.

出版信息

Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13766-9. doi: 10.1073/pnas.93.24.13766.

DOI:10.1073/pnas.93.24.13766
PMID:8943009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC19419/
Abstract

DNA replication is an asymmetric process involving concurrent DNA synthesis on leading and lagging strands. Leading strand synthesis proceeds concomitantly with fork opening, whereas synthesis of the lagging strand essentially takes place on a single-stranded template. The effect of this duality on DNA damage processing by the cellular replication machinery was tested using eukaryotic cell extracts and model DNA substrates containing site-specific DNA adducts formed by the anticancer drug cisplatin or by the carcinogen N-2-acetylaminofluorene. Bypass of both lesions was observed only with fork-like substrates, whereas complete inhibition of DNA synthesis occurred on damaged single-stranded DNA substrates. These results suggest a role for additional accessory factors that permit DNA polymerases to bypass lesions when present in fork-like DNA.

摘要

DNA复制是一个不对称过程，涉及前导链和后随链上的同时DNA合成。前导链合成与复制叉打开同时进行，而后随链的合成基本上发生在单链模板上。利用真核细胞提取物和含有由抗癌药物顺铂或致癌物N-2-乙酰氨基芴形成的位点特异性DNA加合物的模型DNA底物，测试了这种双重性对细胞复制机制处理DNA损伤的影响。仅在叉状底物上观察到两种损伤的绕过，而在受损的单链DNA底物上发生了DNA合成的完全抑制。这些结果表明，当存在于叉状DNA中时，额外的辅助因子可使DNA聚合酶绕过损伤。

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