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

Kevin M Doherty,Sudha Sharma,Laura A Uzdilla,Teresa M Wilson,Sheng Cui,Alessandro Vindigni,Robert M Brosh

doi:10.1074/jbc.m500265200

Abstract

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.

Highlights

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
To gain insight into the molecular functions of RECQ1, we investigated its in vivo protein interactions by co-immunoprecipitation studies and in vitro physical and functional interaction assays
We have identified novel RECQ1 protein interactions with DNA repair factors involved in mismatch correction and DNA recombination

Summary

Introduction

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. 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. A greater understanding of how cells maintain their genome has come from studies in both prokaryotic and eukaryotic organisms These studies have revealed a variety of mechanisms involving DNA transactions performed by DNA replication, repair, and recombination proteins to preserve genomic integrity. No disease has been linked to a mutation in RECQ1, the prominent roles of RecQ helicases in DNA metabolism and maintenance of genomic stability suggest that RECQ1 is likely to have an important biological function. These interactions provide new insight into the role of RECQ1 in the maintenance of the genome

Methods

Results

Conclusion