Replication-mediated disassociation of replication protein A-XPA complex upon DNA damage: implications for RPA handing off.

Cell Biology International
Gaofeng JiangXiaoming Wu

Abstract

RPA (replication protein A), the eukaryotic ssDNA (single-stranded DNA)-binding protein, participates in most cellular processes in response to genotoxic insults, such as NER (nucleotide excision repair), DNA, DSB (double-strand break) repair and activation of cell cycle checkpoint signalling. RPA interacts with XPA (xeroderma pigmentosum A) and functions in early stage of NER. We have shown that in cells the RPA-XPA complex disassociated upon exposure of cells to high dose of UV irradiation. The dissociation required replication stress and was partially attributed to tRPA hyperphosphorylation. Treatment of cells with CPT (camptothecin) and HU (hydroxyurea), which cause DSB DNA damage and replication fork collapse respectively and also leads to the disruption of RPA-XPA complex. Purified RPA and XPA were unable to form complex in vitro in the presence of ssDNA. We propose that the competition-based RPA switch among different DNA metabolic pathways regulates the dissociation of RPA with XPA in cells after DNA damage. The biological significances of RPA-XPA complex disruption in relation with checkpoint activation, DSB repair and RPA hyperphosphorylation are discussed.

References

Dec 1, 1996·Nucleic Acids Research·M SaijoK Tanaka
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·N A AbramovaR Li
May 16, 1998·The Journal of Biological Chemistry·E StiggerS H Lee
Sep 3, 1999·Critical Reviews in Biochemistry and Molecular Biology·C IftodeJ A Borowiec
Mar 15, 2002·Current Opinion in Genetics & Development·Christophe RedonWilliam Bonner
Sep 17, 2002·Genes & Development·Patrick J LupardusKarlene A Cimprich
Oct 23, 2002·Biochemistry·Zheng-guan YangYue Zou
Mar 19, 2003·Biochemistry·Gregory G OakleyKathleen Dixon
Jun 7, 2003·Science·Lee Zou, Stephen J Elledge
Aug 13, 2003·The Journal of Biological Chemistry·Patrick SungMichael G Sehorn
Sep 2, 2003·Molecular Carcinogenesis·Brian S Thoma, Karen M Vasquez
Nov 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lee ZouStephen J Elledge
Jan 17, 2004·Biochimie·Renata M A CostaCarlos F M Menck
Jun 8, 2004·The Journal of Biological Chemistry·Jacob G RobisonGregory G Oakley
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jun-Hyuk ChoiAziz Sancar
Jul 31, 2010·Molecular Cell·Wei Fan, Jianyuan Luo
Jul 23, 2011·Molecular Cell·Shizhou LiuLee Zou

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