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Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest
Bloom's syndrome is a rare autosomal recessive genetic disorder characterized by chromosomal aberrations, genetic instability, and cancer predisposition, all of which may be the result of abnormal signal transduction during DNA damage recognition. Here, we show that BLM is an intermediate respo...
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/PMC2172115/ https://www.ncbi.nlm.nih.gov/pubmed/15364958 http://dx.doi.org/10.1083/jcb.200405128 |
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author | Sengupta, Sagar Robles, Ana I. Linke, Steven P. Sinogeeva, Natasha I. Zhang, Ran Pedeux, Remy Ward, Irene M. Celeste, Arkady Nussenzweig, André Chen, Junjie Halazonetis, Thanos D. Harris, Curtis C. |
author_facet | Sengupta, Sagar Robles, Ana I. Linke, Steven P. Sinogeeva, Natasha I. Zhang, Ran Pedeux, Remy Ward, Irene M. Celeste, Arkady Nussenzweig, André Chen, Junjie Halazonetis, Thanos D. Harris, Curtis C. |
author_sort | Sengupta, Sagar |
collection | PubMed |
description | Bloom's syndrome is a rare autosomal recessive genetic disorder characterized by chromosomal aberrations, genetic instability, and cancer predisposition, all of which may be the result of abnormal signal transduction during DNA damage recognition. Here, we show that BLM is an intermediate responder to stalled DNA replication forks. BLM colocalized and physically interacted with the DNA damage response proteins 53BP1 and H2AX. Although BLM facilitated physical interaction between p53 and 53BP1, 53BP1 was required for efficient accumulation of both BLM and p53 at the sites of stalled replication. The accumulation of BLM/53BP1 foci and the physical interaction between them was independent of γ-H2AX. The active Chk1 kinase was essential for both the accurate focal colocalization of 53BP1 with BLM and the consequent stabilization of BLM. Once the ATR/Chk1- and 53BP1-mediated signal from replicational stress is received, BLM functions in multiple downstream repair processes, thereby fulfilling its role as a caretaker tumor suppressor. |
format | Text |
id | pubmed-2172115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21721152008-03-05 Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest Sengupta, Sagar Robles, Ana I. Linke, Steven P. Sinogeeva, Natasha I. Zhang, Ran Pedeux, Remy Ward, Irene M. Celeste, Arkady Nussenzweig, André Chen, Junjie Halazonetis, Thanos D. Harris, Curtis C. J Cell Biol Research Articles Bloom's syndrome is a rare autosomal recessive genetic disorder characterized by chromosomal aberrations, genetic instability, and cancer predisposition, all of which may be the result of abnormal signal transduction during DNA damage recognition. Here, we show that BLM is an intermediate responder to stalled DNA replication forks. BLM colocalized and physically interacted with the DNA damage response proteins 53BP1 and H2AX. Although BLM facilitated physical interaction between p53 and 53BP1, 53BP1 was required for efficient accumulation of both BLM and p53 at the sites of stalled replication. The accumulation of BLM/53BP1 foci and the physical interaction between them was independent of γ-H2AX. The active Chk1 kinase was essential for both the accurate focal colocalization of 53BP1 with BLM and the consequent stabilization of BLM. Once the ATR/Chk1- and 53BP1-mediated signal from replicational stress is received, BLM functions in multiple downstream repair processes, thereby fulfilling its role as a caretaker tumor suppressor. The Rockefeller University Press 2004-09-13 /pmc/articles/PMC2172115/ /pubmed/15364958 http://dx.doi.org/10.1083/jcb.200405128 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 | Research Articles Sengupta, Sagar Robles, Ana I. Linke, Steven P. Sinogeeva, Natasha I. Zhang, Ran Pedeux, Remy Ward, Irene M. Celeste, Arkady Nussenzweig, André Chen, Junjie Halazonetis, Thanos D. Harris, Curtis C. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest |
title | Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest |
title_full | Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest |
title_fullStr | Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest |
title_full_unstemmed | Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest |
title_short | Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest |
title_sort | functional interaction between blm helicase and 53bp1 in a chk1-mediated pathway during s-phase arrest |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172115/ https://www.ncbi.nlm.nih.gov/pubmed/15364958 http://dx.doi.org/10.1083/jcb.200405128 |
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