Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published June 21, 2004 | Published
Journal Article Open

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

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 III{alpha} (Xtop3{alpha}) 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 Xtop3{alpha} 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.

Additional Information

© The Rockefeller University Press, 2004 Submitted: 18 February 2004; Accepted: 11 May 2004; Published online June 14, 2004. We thank our colleagues in the lab for helpful comments on the manuscript. S.-M. Kim and J. Lee are associates and W.G. Dunphy is an investigator in the Howard Hughes Medical Institute.

Attached Files

Published - LIWjcb04.pdf

Files

LIWjcb04.pdf
Files (2.8 MB)
Name Size Download all
md5:a6b28c06fb93da6a910eaf1f5e345814
2.8 MB Preview Download

Additional details

Created:
August 22, 2023
Modified:
October 13, 2023