RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination.
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.
Doherty
Kevin M
KM
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.
Sharma
Sudha
S
Uzdilla
Laura A
LA
Wilson
Teresa M
TM
Cui
Sheng
S
Vindigni
Alessandro
A
Brosh
Robert M
RM
D000251:Adenosine Triphosphatases / Q000502:physiology*; D015153:Blotting, Western; D004247:DNA / Q000737:chemistry; D004265:DNA Helicases / Q000502:physiology*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005090:Exodeoxyribonucleases / Q000378:metabolism; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051718:MutS Homolog 2 Protein; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D053484:RecQ Helicases; D011994:Recombinant Proteins / Q000737:chemistry; D011995:Recombination, Genetic
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D004247:DNA; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; D000251:Adenosine Triphosphatases; C506731:RECQL4 protein, human; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D004265:DNA Helicases; D053484:RecQ Helicases; D045643:DNA Repair Enzymes