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首页> 外文期刊>Biochemistry >Nucleotide Excision Repair of a DNA Interstrand Cross-Link Produces Single- and Double-Strand Breaks
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Nucleotide Excision Repair of a DNA Interstrand Cross-Link Produces Single- and Double-Strand Breaks

机译：DNA链间交联的核苷酸切除修复产生单链和双链断裂。

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摘要

The DNA radical resulting from formal abstraction of a hydrogen atom from the thymidinenmethyl group, 5-(20n-deoxyuridinyl)methyl radical, forms interstrand cross-links with the opposing 20n-deoxy-nadenosine. This is the first chemically characterized, radical-mediated cross-link between two opposingnnucleotides. In addition, cross-linking between opposing bases in the duplex is less common than betweennthose separated by one or two nucleotides. The first step in cross-link repair was investigated using thenUvrABC bacterial nucleotide excision repair system. UvrABC incised both strands of the cross-linked DNA,nalthough the strand containing the cross-linked purine was preferred by the enzyme in two different duplexes.nThe incision sites in one strand were spaced 11-14 nucleotides apart, as is typical for UvrABC incision. Thenmajority of incisions occur at the third phosphate from the 30n-side of the cross-link and eighth or ninthnphosphate on the 50n-side. In addition, cleavage was found to occur on both strands, producing double-strandnbreaks in ∼25-29% of the incision events. This is the first example of double-strand cleavage duringnnucleotide excision repair of cross-linked DNA that does not already contain a strand break in the vicinitynof the cross-link.
机译：由胸腺嘧啶甲基中的氢原子形式的5-（20n-脱氧尿苷基）甲基自由基形式抽象而来的DNA自由基与相对的20n-脱氧萘腺苷形成链间交联。这是两个相反的核苷酸之间第一个化学表征的，自由基介导的交联。另外，双链体中相对碱基之间的交联不如被一个或两个核苷酸分隔的那些之间的交联。使用thenUvrABC细菌核苷酸切除修复系统研究了交联修复的第一步。 UvrABC切割了交联DNA的两条链，尽管该酶在两个不同的双链体中都优选包含交联嘌呤的链.n一条链中的切割位点间隔11-14个核苷酸，这是UvrABC切割的典型特征。然后大多数切口发生在交联点30n侧的第三个磷酸盐处，而50n侧的第八个或磷酸正丁酯处。此外，发现在两条链上均发生切割，在约25-29％的切口事件中产生双链断裂。这是交联的DNA的核苷酸切除修复期间双链裂解的第一个例子，该交联的DNA在交联附近不包含链断裂。

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  • 来源
    《Biochemistry》 |2010年第1期|p.11-19|共9页
  • 作者

    Xiaohua Peng Avik K. Ghosh Bennett Van Houten and Marc M. Greenberg*;

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    ‡Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218 and §Laboratory ofMolecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park,North Carolina 27709.) Current address: Department of Pharmacology and Chemical Biology, Hillman Cancer Center,5117 Centre Ave., Suite 2.6, Pittsburgh, PA 15213.;

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