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J. Biol. Chem., Vol. 280, Issue 30, 28085-28094, July 29, 2005

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RECQ1 Helicase Interacts with Human Mismatch Repair Factors That Regulate Genetic Recombination^*

Kevin M. Doherty, Sudha Sharma, Laura A. Uzdilla, Teresa M. Wilson, Sheng Cui¶, Alessandro Vindigni¶, and Robert M. Brosh, Jr.||

From the Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland, Baltimore, Maryland 21201, and ^¶International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy

Understanding the molecular and cellular functions of RecQ helicases has attracted considerable interest since several human diseases characterized by premature aging and/or cancer have been genetically linked to mutations in genes of the RecQ family. Although a human disease has not yet been genetically linked to a mutation in RECQ1, the prominent roles of RecQ helicases in the maintenance of genome stability suggest that RECQ1 helicase is likely to be important in vivo.To acquire a better understanding of RECQ1 cellular and molecular functions, we have investigated its protein interactions. Using a co-immunoprecipitation approach, we have identified several DNA repair factors that are associated with RECQ1 in vivo. Direct physical interaction of these repair factors with RECQ1 was confirmed with purified recombinant proteins. Importantly, RECQ1 stimulates the incision activity of human exonuclease 1 and the mismatch repair recognition complex MSH2/6 stimulates RECQ1 helicase activity. These protein interactions suggest a role of RECQ1 in a pathway involving mismatch repair factors. Regulation of genetic recombination, a proposed role for RecQ helicases, is supported by the identified RECQ1 protein interactions and is discussed.

Received for publication, January 7, 2005 , and in revised form, May 6, 2005.

^* This work was supported in part by National Institutes of Health Grant CA095690 (to T. M. W.) and Human Frontier Science Program grant, Fondo gli investmenti della Ricera di Base grant of Ministero dell'Istruzione dell'Universita e della Ricerca, and Consiglio Nazionale delle Ricerche, (Rome) Grant 02.00648.ST97 (to A. V.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Fig. 1.

^|| To whom correspondence should be addressed: Laboratory of Molecular Gerontology, NIA, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224. Tel.: 410-558-8578; Fax: 410-558-8157; E-mail: BroshR{at}grc.nia.nih.gov.

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