title: The Werner and Bloom syndrome proteins catalyze regression of a model replication fork.
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.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0305, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Machwe
authors.forename: Liren
authors.initials: L
authors.lastname: Xiao
authors.forename: Joanna
authors.initials: J
authors.lastname: Groden
authors.forename: David K
authors.initials: DK
authors.lastname: Orren
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D002384:Catalysis; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D004261:DNA Replication / Q000502:physiology*; D005090:Exodeoxyribonucleases; D006801:Humans; D053484:RecQ Helicases / Q000378:metabolism / Q000502:physiology*; D000071657:Werner Syndrome Helicase
chemical_list: D017931:DNA Primers; D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase