Binding and melting of D-loops by the Bloom syndrome helicase Journal Article
| Authors: | van Brabant, A. J.; Ye, T.; Sanz, M.; German, J. L. 3rd; Ellis, N. A.; Holloman, W. K. |
| Article Title: | Binding and melting of D-loops by the Bloom syndrome helicase |
| 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. |
| Keywords: | gene mutation; dna-binding proteins; nonhuman; dna replication; animal cell; dna damage; sister chromatid; protein binding; genetic recombination; recombination, genetic; substrate specificity; models, genetic; conformational transition; helicase; nucleic acid conformation; protein family; genetic predisposition; adenosine triphosphatases; dna helicases; autosomal recessive disorder; rad51 recombinase; structural gene; nucleic acid heteroduplexes; bloom syndrome; humans; priority journal; article |
| Journal Title: | Biochemistry |
| Volume: | 39 |
| Issue: | 47 |
| ISSN: | 0006-2960 |
| Publisher: | American Chemical Society |
| Date Published: | 2000-11-28 |
| Start Page: | 14617 |
| End Page: | 14625 |
| Language: | English |
| DOI: | 10.1021/bi0018640 |
| PUBMED: | 11087418 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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