XRCC1 Coordinates Disparate Responses and Multiprotein Repair Complexes Depending on the Nature and Context of the DNA Damage
XRCC1 Coordinates Disparate Responses and Multiprotein Repair Complexes Depending on the Nature and Context of the DNA Damage
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DOI：
10.1002/em.20663
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发表时间：
2011-10-01
影响因子：
2.8
通讯作者：
Otterlei, Marit
中科院分区：
文献类型：
--
作者：
Hanssen-Bauer, Audun;Solvang-Garten, Karin;Otterlei, Marit
XRCC1 是一种支架蛋白，能够与多种 DNA 修复蛋白相互作用。在这里，我们提供了 XRCC1 在 200 至 1500 kDa 大小的不同复合物中存在的证据，并且我们表明使用 XRCC1 作为诱饵的免疫沉淀能够通过短补丁 (SP) 和长补丁 (LP) 碱基切除修复 (BER) 完全修复 AP 位点。我们表明，POL beta 和 PNK 与 XRCC1 复制灶共定位，并且当应用低剂量的 DNA 损伤剂时，POL beta 和 PNK（而不是 PCNA）与组成型存在的 XRCC1 灶以及损伤诱导灶共定位。我们证明，用于引入 DNA 损伤的激光剂量决定了所招募的 DNA 修复蛋白的组成。此外，我们证明，POL β 和 PNK 招募到低激光剂量照射的区域需要 XRCC1，并且 PARP 抑制剂对 PARylation 的抑制仅略微减少 XRCC1、PNK 或 POL β 招募到 DNA 损伤位点。 PCNA 和 FEN-1 的募集需要更高剂量的照射，XRCC1 以及 PARP-1 在 DNA 损伤部位的积累会增强这种作用。这些数据提高了我们对 BER 蛋白招募到 DNA 损伤位点的理解，并为 XRCC1 在将 BER 组织成不同大小的多蛋白复合物中的作用提供了证据。环境。摩尔。诱变剂。 52:623-635, 2011。(C) 2011 Wiley 期刊公司。
XRCC1 is a scaffold protein capable of interacting with several DNA repair proteins. Here we provide evidence for the presence of XRCC1 in different complexes of sizes from 200 to 1500 kDa, and we show that immunoprecipitates using XRCC1 as bait are capable of complete repair of AP sites via both short patch (SP) and long patch (LP) base excision repair (BER). We show that POL beta and PNK colocalize with XRCC1 in replication foci and that POL beta and PNK, but not PCNA, colocalize with constitutively present XRCC1-foci as well as damage-induced foci when low doses of a DNA-damaging agent are applied. We demonstrate that the laser dose used for introducing DNA damage determines the repertoire of DNA repair proteins recruited. Furthermore, we demonstrate that recruitment of POL beta and PNK to regions irradiated with low laser dose requires XRCC1 and that inhibition of PARylation by PARP-inhibitors only slightly reduces the recruitment of XRCC1, PNK, or POL beta to sites of DNA damage. Recruitment of PCNA and FEN-1 requires higher doses of irradiation and is enhanced by XRCC1, as well as by accumulation of PARP-1 at the site of DNA damage. These data improve our understanding of recruitment of BER proteins to sites of DNA damage and provide evidence for a role of XRCC1 in the organization of BER into multiprotein complexes of different sizes. Environ. Mol. Mutagen. 52:623-635, 2011. (C) 2011 Wiley Periodicals, Inc.