Delayed DNA joining at 3′ mismatches by human DNA ligases
Delayed DNA joining at 3′ mismatches by human DNA ligases
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DOI：
10.1093/nar/27.20.4028
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发表时间：
1999-10-15
影响因子：
14.9
通讯作者：
Lindahl, T
中科院分区：
文献类型：
--
作者：
Bhagwat, AS;Sanderson, RJ;Lindahl, T
DNA聚合酶β催化的修复合成发生在哺乳动物碱基切除修复的主要途径中，DNA聚合酶β不具有核外溶解校对能力，在DNA合成过程中出现错误的频率很高。因此，通过短补丁修复合成持续纠正内源DNA损伤可能会导致较高的自发突变率，除非修复途径中的后续步骤允许选择性地去除掺入错误。我们在这里表明，当在生理浓度的KCl存在下进行检测时，人类DNA连接酶I和III都强烈区分DNA中缺口3‘位置的正确配对残基和错配残基。在缺口填充过程中，DNA聚合酶β错误结合后导致的连接延迟可能允许通过不同的3‘外切酶去除不匹配的末端残基。
Repair synthesis catalysed by DNA polymerase beta at 1 nt gaps occurs in the main pathway of mammalian base excision repair, DNA polymerase beta has no exonucleolytic proof-reading ability, and exhibits high error frequency during DNA synthesis. Consequently, continuous correction of endogenous DNA damage by short-patch repair synthesis might lead to a high spontaneous mutation rate, unless subsequent steps in the repair pathway allow for selective removal of incorporation errors. We show here that both human DNA ligase I and III discriminate strongly between a correctly paired versus a mispaired residue at the 3' position of a nick in DNA, when assayed in the presence of physiological concentrations of KCl. The resulting delay in joining after misincorporation by DNA polymerase beta during gap filling could allow for removal of the mismatched terminal residue by a distinct 3' exonuclease.