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

TitleBinding and melting of D-loops by the Bloom syndrome helicase.
Publication TypeJournal Article
Year of Publication2000
Authorsvan Brabant AJ, Ye T, Sanz M, III JLGerman, Ellis NA, Holloman WK
Date Published2000 Nov 28
KeywordsAdenosine Triphosphatases, Bloom Syndrome, DNA Damage, DNA Helicases, DNA-Binding Proteins, Humans, Models, Genetic, Nucleic Acid Conformation, Nucleic Acid Heteroduplexes, Protein Binding, Rad51 Recombinase, Recombination, Genetic, RecQ Helicases, Substrate Specificity

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.

Alternate JournalBiochemistry
PubMed ID11087418
Grant ListCA50897 / CA / NCI NIH HHS / United States
GM42482 / GM / NIGMS NIH HHS / United States

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