title: Direct interaction between XRCC1 and UNG2 facilitates rapid repair of uracil in DNA by XRCC1 complexes.
abstract: 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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Mansour
authors.initials: M
authors.lastname: Akbari
authors.forename: Karin
authors.initials: K
authors.lastname: Solvang-Garten
authors.forename: Audun
authors.initials: A
authors.lastname: Hanssen-Bauer
authors.forename: Nora Valeska
authors.initials: NV
authors.lastname: Lieske
authors.forename: Henrik Sahlin
authors.initials: HS
authors.lastname: Pettersen
authors.forename: Grete Klippenvåg
authors.initials: GK
authors.lastname: Pettersen
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
authors.forename: Hans E
authors.initials: HE
authors.lastname: Krokan
authors.forename: Marit
authors.initials: M
authors.lastname: Otterlei
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics / Q000378:metabolism; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D014498:Uracil / Q000378:metabolism*; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D014498:Uracil; D004247:DNA; C492570:CCNO protein, human; D045647:DNA Glycosylases
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