An Alternative Form of Replication Protein A Expressed in Normal Human Tissues Supports DNA Repair

Michael G Kemp; Aaron C Mason; Aura Carreira; Joyce T Reardon; Stuart J Haring; Gloria E. O Borgstahl; Stephen C Kowalczykowski; Aziz Sancar; Marc S Wold

doi:10.1074/jbc.M109.079418

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An Alternative Form of Replication Protein A Expressed in Normal Human Tissues Supports DNA Repair

Journal article

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An Alternative Form of Replication Protein A Expressed in Normal Human Tissues Supports DNA Repair

Michael G Kemp, Aaron C Mason, Aura Carreira, Joyce T Reardon, Stuart J Haring, Gloria E. O Borgstahl, Stephen C Kowalczykowski, Aziz Sancar and Marc S Wold

The Journal of biological chemistry, Vol.285(7), pp.4788-4797

02/12/2010

DOI: 10.1074/jbc.M109.079418

PMCID: PMC2836084

PMID: 19996105

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Abstract

Replication protein A (RPA) is a heterotrimeric protein complex required for a large number of DNA metabolic processes, including DNA replication and repair. An alternative form of RPA (aRPA) has been described in which the RPA2 subunit (the 32-kDa subunit of RPA and product of the RPA2 gene) of canonical RPA is replaced by a homologous subunit, RPA4. The normal function of aRPA is not known; however, previous studies have shown that it does not support DNA replication in vitro or S-phase progression in vivo . In this work, we show that the RPA4 gene is expressed in normal human tissues and that its expression is decreased in cancerous tissues. To determine whether aRPA plays a role in cellular physiology, we investigated its role in DNA repair. aRPA interacted with both Rad52 and Rad51 and stimulated Rad51 strand exchange. We also showed that, by using a reconstituted reaction, aRPA can support the dual incision/excision reaction of nucleotide excision repair. aRPA is less efficient in nucleotide excision repair than canonical RPA, showing reduced interactions with the repair factor XPA and no stimulation of XPF-ERCC1 endonuclease activity. In contrast, aRPA exhibits higher affinity for damaged DNA than canonical RPA, which may explain its ability to substitute for RPA in the excision step of nucleotide excision repair. Our findings provide the first direct evidence for the function of aRPA in human DNA metabolism and support a model for aRPA functioning in chromosome maintenance functions in nonproliferating cells.

DNA and Chromosomes

Recombination

Gene

Transcription

DNA

Replication

Repair

Replication Protein A

Cancer

Details

Title: Subtitle: An Alternative Form of Replication Protein A Expressed in Normal Human Tissues Supports DNA Repair
Creators: Michael G Kemp - From the
Aaron C Mason - the
Aura Carreira - the
Joyce T Reardon - From the
Stuart J Haring - the
Gloria E. O Borgstahl - The Eppley Institute, Nebraska Medical Center, Omaha, Nebraska 68198
Stephen C Kowalczykowski - the
Aziz Sancar - From the
Marc S Wold - the
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.285(7), pp.4788-4797
DOI: 10.1074/jbc.M109.079418
PMID: 19996105
PMCID: PMC2836084
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: GM32833; GM62653; GM44721 / National Institutes of Health
Language: English
Date published: 02/12/2010
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984024410102771

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