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Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins

The principal microtubule-organizing center in animal cells, the centrosome, contains centrin, a small, conserved calcium-binding protein unique to eukaryotes. Several centrin isoforms exist and have been implicated in various cellular processes including nuclear export and deoxyribonucleic acid (DN...

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Autores principales: Dantas, Tiago J., Wang, Yifan, Lalor, Pierce, Dockery, Peter, Morrison, Ciaran G.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080269/
https://www.ncbi.nlm.nih.gov/pubmed/21482720
http://dx.doi.org/10.1083/jcb.201012093
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author Dantas, Tiago J.
Wang, Yifan
Lalor, Pierce
Dockery, Peter
Morrison, Ciaran G.
author_facet Dantas, Tiago J.
Wang, Yifan
Lalor, Pierce
Dockery, Peter
Morrison, Ciaran G.
author_sort Dantas, Tiago J.
collection PubMed
description The principal microtubule-organizing center in animal cells, the centrosome, contains centrin, a small, conserved calcium-binding protein unique to eukaryotes. Several centrin isoforms exist and have been implicated in various cellular processes including nuclear export and deoxyribonucleic acid (DNA) repair. Although centrins are required for centriole/basal body duplication in lower eukaryotes, centrin functions in vertebrate centrosome duplication are less clear. To define these roles, we used gene targeting in the hyperrecombinogenic chicken DT40 cell line to delete all three centrin genes in individual clones. Unexpectedly, centrin-deficient cells underwent normal cellular division with no detectable cell cycle defects. Light and electron microscopy analyses revealed no significant difference in centrosome composition or ultrastructure. However, centrin deficiency made DT40 cells highly sensitive to ultraviolet (UV) irradiation, with Cetn3 deficiency exacerbating the sensitivity of Cetn4/Cetn2 double mutants. DNA damage checkpoints were intact, but repair of UV-induced DNA damage was delayed in centrin nulls. These data demonstrate a role for vertebrate centrin in nucleotide excision repair.
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spelling pubmed-30802692011-10-18 Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins Dantas, Tiago J. Wang, Yifan Lalor, Pierce Dockery, Peter Morrison, Ciaran G. J Cell Biol Research Articles The principal microtubule-organizing center in animal cells, the centrosome, contains centrin, a small, conserved calcium-binding protein unique to eukaryotes. Several centrin isoforms exist and have been implicated in various cellular processes including nuclear export and deoxyribonucleic acid (DNA) repair. Although centrins are required for centriole/basal body duplication in lower eukaryotes, centrin functions in vertebrate centrosome duplication are less clear. To define these roles, we used gene targeting in the hyperrecombinogenic chicken DT40 cell line to delete all three centrin genes in individual clones. Unexpectedly, centrin-deficient cells underwent normal cellular division with no detectable cell cycle defects. Light and electron microscopy analyses revealed no significant difference in centrosome composition or ultrastructure. However, centrin deficiency made DT40 cells highly sensitive to ultraviolet (UV) irradiation, with Cetn3 deficiency exacerbating the sensitivity of Cetn4/Cetn2 double mutants. DNA damage checkpoints were intact, but repair of UV-induced DNA damage was delayed in centrin nulls. These data demonstrate a role for vertebrate centrin in nucleotide excision repair. The Rockefeller University Press 2011-04-18 /pmc/articles/PMC3080269/ /pubmed/21482720 http://dx.doi.org/10.1083/jcb.201012093 Text en © 2011 Dantas 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
Dantas, Tiago J.
Wang, Yifan
Lalor, Pierce
Dockery, Peter
Morrison, Ciaran G.
Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
title Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
title_full Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
title_fullStr Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
title_full_unstemmed Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
title_short Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
title_sort defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080269/
https://www.ncbi.nlm.nih.gov/pubmed/21482720
http://dx.doi.org/10.1083/jcb.201012093
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