Binding and melting of D-loops by the Bloom syndrome helicase

A. J. Van Brabant, T. Ye, M. Sanz, J. L. German, N. A. Ellis, W. K. Holloman

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

Bloom syndrome is a rare autosomal disorder characterized by predisposition to cancer and genomic instability. BLM, the structural gene mutated in individuals with the disorder, encodes a DNA helicase belonging to the RecQ family of helicases. These helicases have been established to serve roles in both promoting and preventing recombination. Mounting evidence has implicated a function for BLM during DNA replication; specifically, BLM might be involved in rescuing stalled or collapsed replication forks by a recombination-based mechanism. We have tested this idea by examining the binding and melting activity of BLM on oligonucleotide substrates containing D-loops, DNA structures that model the presumed initial intermediate formed during homologous recombination. We find that BLM preferentially melts those D-loops that are formed more favorably by the strand exchange protein Rad51, but whose polarity could be less favorable for enabling restoration of an active replication fork. We propose a model in which BLM selectively dissociates recombination intermediates likely to be unfavorable for recombination-promoted replication.

Original languageEnglish (US)
Pages (from-to)14617-14625
Number of pages9
JournalBiochemistry
Volume39
Issue number47
DOIs
StatePublished - Nov 28 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Van Brabant, A. J., Ye, T., Sanz, M., German, J. L., Ellis, N. A., & Holloman, W. K. (2000). Binding and melting of D-loops by the Bloom syndrome helicase. Biochemistry, 39(47), 14617-14625. https://doi.org/10.1021/bi0018640