The Werner and Bloom Syndrome Proteins Catalyze Regression of a Model Replication Fork
The premature aging and cancer-prone diseases Werner and Bloom syndromes are caused by loss of function of WRN and BLM proteins, respectively. At the cellular level, WRN or BLM deficiency causes replication abnormalities, DNA damage hypersensitivity, and genome instability, suggesting that these pro...
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Published in | Biochemistry (Easton) Vol. 45; no. 47; pp. 13939 - 13946 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
28.11.2006
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Subjects | |
Online Access | Get full text |
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Summary: | The premature aging and cancer-prone diseases Werner and Bloom syndromes are caused by loss of function of WRN and BLM proteins, respectively. At the cellular level, WRN or BLM deficiency causes replication abnormalities, DNA damage hypersensitivity, and genome instability, suggesting that these proteins might participate in resolution of replication blockage. Although WRN and BLM are helicases belonging to the RecQ family, both have been recently shown to also facilitate pairing of complementary DNA strands. In this study, we demonstrate that both WRN and BLM (but not other selected helicases) can coordinate their unwinding and pairing activities to regress a model replication fork substrate. Notably, fork regression is widely believed to be the initial step in responding to replication blockage. Our findings suggest that WRN and/or BLM might regress replication forks in vivo as part of a genome maintenance pathway, consistent with the phenotypes of WRN- and BLM-deficient cells. |
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Bibliography: | This work was supported by Grant R01 CA113371 to D.K.O. from the National Cancer Institute of the National Institutes of Health. istex:5E1D633E12A4E7757A1964746044FA4E809E8507 ark:/67375/TPS-BDJ90RWX-N ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/bi0615487 |