Direct interaction between XRCC1 and UNG2 facilitates rapid repair of uracil in DNA by XRCC1 complexes

被引：48

作者：

Akbari, Mansour ^{[1
]}

Solvang-Garten, Karin ^{[1
]}

Hanssen-Bauer, Audun ^{[1
]}

Lieske, Nora Valeska ^{[1
]}

Pettersen, Henrik Sahlin ^{[1
]}

Pettersen, Grete Klippenvag ^{[1
]}

Wilson, David M., III ^{[2
]}

Krokan, Hans E. ^{[1
]}

Otterlei, Marit ^{[1
]}

机构：

[1] Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway

[2] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA

来源：

DNA REPAIR | 2010年 / 9卷 / 07期

关键词：

Base excision repair; XRCC1; UNG2; DNA repair complexes; Replication associated repair; BASE EXCISION-REPAIR; STRAND-BREAK REPAIR; SISTER-CHROMATID EXCHANGE; POLY(ADP-RIBOSE) POLYMERASE; PHYSICALLY INTERACTS; MOLECULAR-CLONING; REPLICATION FOCI; CELL-EXTRACTS; LIGASE-III; IN-VITRO;

D O I：

10.1016/j.dnarep.2010.04.002

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Uracil-DNA glycosylase, UNG2, interacts with PCNA and initiates post-replicative base excision repair (BER) of uracil in DNA. The DNA repair protein XRCC1 also co-localizes and physically interacts with PCNA. However, little is known about whether UNG2 and XRCC1 directly interact and participate in a same complex for repair of uracil in replication foci. Here, we examine localization pattern of these proteins in live and fixed cells and show that UNG2 and XRCC1 are likely in a common complex in replication foci. Using pull-down experiments we demonstrate that UNG2 directly interacts with the nuclear localization signal-region (NLS) of XRCC1. Western blot and functional analysis of immunoprecipitates from whole cell extracts prepared from S-phase enriched cells demonstrate the presence of XRCC1 complexes that contain UNG2 in addition to separate XRCC1 and UNG2 associated complexes with distinct repair features. XRCC1 complexes performed complete repair of uracil with higher efficacy than UNG2 complexes. Based on these results, we propose a model for a functional role of XRCC1 in replication associated BER of uracil. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：785 / 795

页数：11

共 47 条

[1] Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA [J].