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PMID: 15197177 Published · ppublish English Journal Article

Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases.

The Journal of cell biology ·Vol. 165 ·No. 6 ·2004-06-21 ·Pages 801-12

Li W, Kim SM, Lee J, Dunphy WG

Abstract

Bloom's syndrome (BS), a disorder associated with genomic instability and cancer predisposition, results from defects in the Bloom's helicase (BLM) protein. In BS cells, chromosomal abnormalities such as sister chromatid exchanges occur at highly elevated rates. Using Xenopus egg extracts, we have studied Xenopus BLM (Xblm) during both unperturbed and disrupted DNA replication cycles. Xblm binds to replicating chromatin and becomes highly phosphorylated in the presence of DNA replication blocks. This phosphorylation depends on Xenopus ATR (Xatr) and Xenopus Rad17 (Xrad17), but not Claspin. Xblm and Xenopus topoisomerase IIIalpha (Xtop3alpha) interact in a regulated manner and associate with replicating chromatin interdependently. Immunodepletion of Xblm from egg extracts results in accumulation of chromosomal DNA breaks during both normal and perturbed DNA replication cycles. Disruption of the interaction between Xblm and Xtop3alpha has similar effects. The occurrence of DNA damage in the absence of Xblm, even without any exogenous insult to the DNA, may help to explain the genesis of chromosomal defects in BS cells.

MeSH Terms
Adenosine Triphosphatases/deficiency,genetics Animals Bloom Syndrome/genetics Cell Nucleus/physiology,ultrastructure Chromatin/physiology,ultrastructure DNA Damage DNA Helicases/deficiency,genetics Female Humans Male Methionine/metabolism Ovum/cytology RecQ Helicases S Phase/genetics,physiology Spermatozoa/cytology Xenopus
Chemicals
Chromatin Methionine Adenosine Triphosphatases Bloom syndrome protein DNA Helicases RecQ Helicases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Li Wenhui
Division of Biology 216-76, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA.
Kim Soo-Mi
Lee Joon
Dunphy William G
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200402095
Published
2004-06-21
Epub
2004-00-14
Pages
801-12
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172405
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200402095 PMC Full Text View journal details
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