Role for BLM in replication-fork restart and suppression of origin firing after replicative stress

Sally L Davies; Phillip S North; Ian D Hickson

doi:10.1038/nsmb1267

Role for BLM in replication-fork restart and suppression of origin firing after replicative stress

Nat Struct Mol Biol. 2007 Jul;14(7):677-9. doi: 10.1038/nsmb1267. Epub 2007 Jun 24.

Authors

Sally L Davies¹, Phillip S North, Ian D Hickson

Affiliation

¹ Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.

PMID: 17603497
DOI: 10.1038/nsmb1267

Abstract

Mutations in BLM give rise to Bloom's syndrome, a genetic disorder associated with cancer predisposition and chromosomal instability. Using a dual-labeling system in isolated chromosome fibers, we show that the BLM protein is required for two aspects of the cellular response to replicative stress: efficient replication-fork restart and suppression of new origin firing. These functions require the helicase activity of BLM and the Thr99 residue targeted by stress-activated kinases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / physiology*
Cells, Cultured
DNA Helicases / genetics
DNA Helicases / physiology*
DNA Replication* / drug effects
Humans
Protein Serine-Threonine Kinases / metabolism
RecQ Helicases
Replication Origin*
Threonine / metabolism

Substances

Threonine
Protein Serine-Threonine Kinases
Adenosine Triphosphatases
Bloom syndrome protein
DNA Helicases
RecQ Helicases