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Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases
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,...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172405/ https://www.ncbi.nlm.nih.gov/pubmed/15197177 http://dx.doi.org/10.1083/jcb.200402095 |
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author | Li, Wenhui Kim, Soo-Mi Lee, Joon Dunphy, William G. |
author_facet | Li, Wenhui Kim, Soo-Mi Lee, Joon Dunphy, William G. |
author_sort | Li, Wenhui |
collection | PubMed |
description | 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 IIIα (Xtop3α) 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 Xtop3α 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. |
format | Text |
id | pubmed-2172405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21724052008-03-05 Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases Li, Wenhui Kim, Soo-Mi Lee, Joon Dunphy, William G. J Cell Biol Article 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 IIIα (Xtop3α) 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 Xtop3α 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. The Rockefeller University Press 2004-06-21 /pmc/articles/PMC2172405/ /pubmed/15197177 http://dx.doi.org/10.1083/jcb.200402095 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Li, Wenhui Kim, Soo-Mi Lee, Joon Dunphy, William G. Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases |
title | Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases |
title_full | Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases |
title_fullStr | Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases |
title_full_unstemmed | Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases |
title_short | Absence of BLM leads to accumulation of chromosomal DNA breaks during both unperturbed and disrupted S phases |
title_sort | absence of blm leads to accumulation of chromosomal dna breaks during both unperturbed and disrupted s phases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172405/ https://www.ncbi.nlm.nih.gov/pubmed/15197177 http://dx.doi.org/10.1083/jcb.200402095 |
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