Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1

Sudha Sharma, Joshua A. Sommers, Saba Choudhary, Jinnifer Korin Faulkner, Sheng Cui, Lucia Andreoli, Laura Muzzolini, Alessandro Vindigni, Robert M. Brosh

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

RecQ helicases play an important role in preserving genomic integrity, and their cellular roles in DNA repair, recombination, and replication have been of considerable interest. Of the five human RecQ helicases identified, three are associated with genetic disorders characterized by an elevated incidence of cancer or premature aging: Werner syndrome, Bloom syndrome, and Rothmund-Thomson syndrome. Although the biochemical properties and protein interactions of the WRN and BLM helicases defective in Werner syndrome and Bloom syndrome, respectively, have been extensively investigated, less information is available concerning the functions of the other human RecQ helicases. We have focused our attention on human RECQ1, a DNA helicase whose cellular functions remain largely uncharacterized. In this work, we have characterized the DNA substrate specificity and optimal cofactor requirements for efficient RECQl-catalyzed DNA unwinding and determined that RECQ1 has certain properties that are distinct from those of other RecQ helicases. RECQ1 stably bound to a variety of DNA structures, enabling it to unwind a diverse set of DNA substrates. In addition to its DNA binding and helicase activities, RECQ1 catalyzed efficient strand annealing between complementary single-stranded DNA molecules. The ability of RECQ1 to promote strand annealing was modulated by ATP binding, which induced a conformational change in the protein. The enzymatic properties of the RECQ1 helicase and strand annealing activities are discussed in the context of proposed cellular DNA metabolic pathways that are important in the maintenance of genomic stability.

Original languageEnglish
Pages (from-to)28072-28084
Number of pages13
JournalJournal of Biological Chemistry
Volume280
Issue number30
DOIs
StatePublished - Jul 29 2005

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