Extracts of proliferating and non-proliferating human cells display different base excision pathways and repair fidelity
Extracts of proliferating and non-proliferating human cells display different base excision pathways and repair fidelity
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DOI：
10.1016/j.dnarep.2009.04.002
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发表时间：
2009-07-04
期刊：
影响因子：
3.8
通讯作者：
Krokan, Hans Einar
中科院分区：
文献类型：
--
作者：
Akbari, Mansour;Pena-Diaz, Javier;Krokan, Hans Einar
据报道，DNA中受损或不合适碱基的碱基切除修复（BER）可以通过单个核苷酸插入或几个核苷酸的结合进行，分别称为短补丁和长补丁修复。我们发现来自增殖和非增殖细胞的提取物都具有单核苷酸和双核苷酸插入BER活性的能力。然而，大于两个核苷酸的斑块大小仅在增殖细胞的提取物中检测到。与来自增殖细胞的提取物相比，来自非增殖细胞的提取物的POL β浓度大约高出两倍，这是导致大部分双核苷酸插入BER的原因。相比之下，增殖细胞提取物中的双核苷酸插入不依赖于POL β。与增殖细胞的提取物相比，非增殖细胞提取物的BER保真度低两到三倍。此外，尽管单核苷酸缺失是两种提取物中主要的修复错误类型，但修复错误的模式有所不同。这些结果表明，在非增殖细胞中，双核苷酸贴片BER是一种独特的POL β依赖机制，并且表明与增殖细胞相比，非增殖细胞提取物中的BER保真度较低。(C) 2009 Elsevier B.V.版权所有
Base excision repair (BER) of damaged or inappropriate bases in DNA has been reported to take place by single nucleotide insertion or through incorporation of several nucleotides, termed short-patch and long-patch repair, respectively. We found that extracts from proliferating and non-proliferating cells both had capacity for single- and two-nucleotide insertion BER activity. However, patch size longer than two nucleotides was only detected in extracts from proliferating cells. Relative to extracts from proliferating cells, extracts from non-proliferating cells had approximately two-fold higher concentration of POL beta, which contributed to most of two-nucleotide insertion BER. In contrast, two-nucleotide insertion in extracts from proliferating cells was not dependent on POL beta. BER fidelity was two- to three-fold lower in extracts from the non-proliferating compared with extracts of proliferating cells. Furthermore, although one-nucleotide deletion was the predominant type of repair error in both extracts, the pattern of repair errors was somewhat different. These results establish two-nucleotide patch BER as a distinct POL beta-dependent mechanism in non-proliferating cells and demonstrate that BER fidelity is lower in extracts from non-proliferating as compared with proliferating cells. (C) 2009 Elsevier B.V. All rights reserved.