This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by de Souza-Pinto, N. C.
Right arrow Articles by Bohr, V. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Souza-Pinto, N. C.
Right arrow Articles by Bohr, V. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2009, p. 4441-4454, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.00265-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Recombination Protein RAD52 Cooperates with the Excision Repair Protein OGG1 for the Repair of Oxidative Lesions in Mammalian Cells{triangledown}

Nadja C. de Souza-Pinto,1,2,{dagger} Scott Maynard,1,{dagger} Kazunari Hashiguchi,1,{ddagger} Jingping Hu,1,§ Meltem Muftuoglu,1,¶ and Vilhelm A. Bohr1*

Laboratory of Molecular Gerontology, NIA-IRP, National Institutes of Health, Baltimore, Maryland 21224,1 Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil2

Received 27 February 2009/ Returned for modification 10 April 2009/ Accepted 28 May 2009

Oxidized bases are common types of DNA modifications. Their accumulation in the genome is linked to aging and degenerative diseases. These modifications are commonly repaired by the base excision repair (BER) pathway. Oxoguanine DNA glycosylase (OGG1) initiates BER of oxidized purine bases. A small number of protein interactions have been identified for OGG1, while very few appear to have functional consequences. We report here that OGG1 interacts with the recombination protein RAD52 in vitro and in vivo. This interaction has reciprocal functional consequences as OGG1 inhibits RAD52 catalytic activities and RAD52 stimulates OGG1 incision activity, likely increasing its turnover rate. RAD52 colocalizes with OGG1 after oxidative stress to cultured cells, but not after the direct induction of double-strand breaks by ionizing radiation. Human cells depleted of RAD52 via small interfering RNA knockdown, and mouse cells lacking the protein via gene knockout showed increased sensitivity to oxidative stress. Moreover, cells depleted of RAD52 show higher accumulation of oxidized bases in their genome than cells with normal levels of RAD52. Our results indicate that RAD52 cooperates with OGG1 to repair oxidative DNA damage and enhances the cellular resistance to oxidative stress. Our observations suggest a coordinated action between these proteins that may be relevant when oxidative lesions positioned close to strand breaks impose a hindrance to RAD52 catalytic activities.

* Corresponding author. Mailing address: Laboratory of Molecular Gerontology, NIA-IRP, 251 Bayview Blvd., Ste. 100, Baltimore, MD 21224. Phone: (410) 558-8162. Fax: (410) 558-8157. E-mail: vbohr{at}nih.gov

{triangledown} Published ahead of print on 8 June 2009.

{dagger} N.C.D.S.-P. and S.M. contributed equally to this study.

{ddagger} Present address: Laboratory of Radiation Biology, Graduate School of Science, Kyoto University, Kyoto, Japan.

§ Present address: Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.

Present address: Danish Center for Healthy Ageing, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

Molecular and Cellular Biology, August 2009, p. 4441-4454, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.00265-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»