The Werner and Bloom syndrome proteins catalyze regression of a model replication fork

Amrita Machwe, Liren Xiao, Joanna Groden, David K. Orren

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)13939-13946
Number of pages8
JournalBiochemistry
Volume45
Issue number47
DOIs
StatePublished - Nov 28 2006

ASJC Scopus subject areas

  • Biochemistry

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