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Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination
Bloom’s syndrome (BS) is an autosomal recessive disorder characterized by growth retardation, cancer predisposition, and sterility. BS mutated (Blm), the gene mutated in BS patients, is one of five mammalian RecQ helicases. Although BLM has been shown to promote genome stability by assisting in the...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845075/ https://www.ncbi.nlm.nih.gov/pubmed/20308424 http://dx.doi.org/10.1083/jcb.200909048 |
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author | Holloway, J. Kim Morelli, Meisha A. Borst, Peter L. Cohen, Paula E. |
author_facet | Holloway, J. Kim Morelli, Meisha A. Borst, Peter L. Cohen, Paula E. |
author_sort | Holloway, J. Kim |
collection | PubMed |
description | Bloom’s syndrome (BS) is an autosomal recessive disorder characterized by growth retardation, cancer predisposition, and sterility. BS mutated (Blm), the gene mutated in BS patients, is one of five mammalian RecQ helicases. Although BLM has been shown to promote genome stability by assisting in the repair of DNA structures that arise during homologous recombination in somatic cells, less is known about its role in meiotic recombination primarily because of the embryonic lethality associated with Blm deletion. However, the localization of BLM protein on meiotic chromosomes together with evidence from yeast and other organisms implicates a role for BLM helicase in meiotic recombination events, prompting us to explore the meiotic phenotype of mice bearing a conditional mutant allele of Blm. In this study, we show that BLM deficiency does not affect entry into prophase I but causes severe defects in meiotic progression. This is exemplified by improper pairing and synapsis of homologous chromosomes and altered processing of recombination intermediates, resulting in increased chiasmata. Our data provide the first analysis of BLM function in mammalian meiosis and strongly argue that BLM is involved in proper pairing, synapsis, and segregation of homologous chromosomes; however, it is dispensable for the accumulation of recombination intermediates. |
format | Text |
id | pubmed-2845075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28450752010-09-22 Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination Holloway, J. Kim Morelli, Meisha A. Borst, Peter L. Cohen, Paula E. J Cell Biol Research Articles Bloom’s syndrome (BS) is an autosomal recessive disorder characterized by growth retardation, cancer predisposition, and sterility. BS mutated (Blm), the gene mutated in BS patients, is one of five mammalian RecQ helicases. Although BLM has been shown to promote genome stability by assisting in the repair of DNA structures that arise during homologous recombination in somatic cells, less is known about its role in meiotic recombination primarily because of the embryonic lethality associated with Blm deletion. However, the localization of BLM protein on meiotic chromosomes together with evidence from yeast and other organisms implicates a role for BLM helicase in meiotic recombination events, prompting us to explore the meiotic phenotype of mice bearing a conditional mutant allele of Blm. In this study, we show that BLM deficiency does not affect entry into prophase I but causes severe defects in meiotic progression. This is exemplified by improper pairing and synapsis of homologous chromosomes and altered processing of recombination intermediates, resulting in increased chiasmata. Our data provide the first analysis of BLM function in mammalian meiosis and strongly argue that BLM is involved in proper pairing, synapsis, and segregation of homologous chromosomes; however, it is dispensable for the accumulation of recombination intermediates. The Rockefeller University Press 2010-03-22 /pmc/articles/PMC2845075/ /pubmed/20308424 http://dx.doi.org/10.1083/jcb.200909048 Text en © 2010 Holloway et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Holloway, J. Kim Morelli, Meisha A. Borst, Peter L. Cohen, Paula E. Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination |
title | Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination |
title_full | Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination |
title_fullStr | Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination |
title_full_unstemmed | Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination |
title_short | Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination |
title_sort | mammalian blm helicase is critical for integrating multiple pathways of meiotic recombination |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845075/ https://www.ncbi.nlm.nih.gov/pubmed/20308424 http://dx.doi.org/10.1083/jcb.200909048 |
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