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Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint

During homologous recombination, cells must coordinate repair, DNA damage checkpoint signaling, and movement of chromosomal loci to facilitate homology search. In Saccharomyces cerevisiae, increased movement of damaged loci (local mobility) and undamaged loci (global mobility) precedes homolog pairi...

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Detalles Bibliográficos
Autores principales: Smith, Michael J., Bryant, Eric E., Rothstein, Rodney
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120718/
https://www.ncbi.nlm.nih.gov/pubmed/30181361
http://dx.doi.org/10.1101/gad.317966.118
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author Smith, Michael J.
Bryant, Eric E.
Rothstein, Rodney
author_facet Smith, Michael J.
Bryant, Eric E.
Rothstein, Rodney
author_sort Smith, Michael J.
collection PubMed
description During homologous recombination, cells must coordinate repair, DNA damage checkpoint signaling, and movement of chromosomal loci to facilitate homology search. In Saccharomyces cerevisiae, increased movement of damaged loci (local mobility) and undamaged loci (global mobility) precedes homolog pairing in mitotic cells. How cells modulate chromosome mobility in response to DNA damage remains unclear. Here, we demonstrate that global chromosome mobility is regulated by the Rad51 recombinase and its mediator, Rad52. Surprisingly, rad51Δ rad52Δ cells display checkpoint-dependent constitutively increased mobility, indicating that a regulatory circuit exists between recombination and checkpoint machineries to govern chromosomal mobility. We found that the requirement for Rad51 in this circuit is distinct from its role in recombination and that interaction with Rad52 is necessary to alleviate inhibition imposed by mediator recruitment to ssDNA. Thus, interplay between recombination factors and the checkpoint restricts increased mobility until recombination proteins are assembled at damaged sites.
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spelling pubmed-61207182019-03-01 Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint Smith, Michael J. Bryant, Eric E. Rothstein, Rodney Genes Dev Research Paper During homologous recombination, cells must coordinate repair, DNA damage checkpoint signaling, and movement of chromosomal loci to facilitate homology search. In Saccharomyces cerevisiae, increased movement of damaged loci (local mobility) and undamaged loci (global mobility) precedes homolog pairing in mitotic cells. How cells modulate chromosome mobility in response to DNA damage remains unclear. Here, we demonstrate that global chromosome mobility is regulated by the Rad51 recombinase and its mediator, Rad52. Surprisingly, rad51Δ rad52Δ cells display checkpoint-dependent constitutively increased mobility, indicating that a regulatory circuit exists between recombination and checkpoint machineries to govern chromosomal mobility. We found that the requirement for Rad51 in this circuit is distinct from its role in recombination and that interaction with Rad52 is necessary to alleviate inhibition imposed by mediator recruitment to ssDNA. Thus, interplay between recombination factors and the checkpoint restricts increased mobility until recombination proteins are assembled at damaged sites. Cold Spring Harbor Laboratory Press 2018-09-01 /pmc/articles/PMC6120718/ /pubmed/30181361 http://dx.doi.org/10.1101/gad.317966.118 Text en © 2018 Smith et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Smith, Michael J.
Bryant, Eric E.
Rothstein, Rodney
Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint
title Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint
title_full Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint
title_fullStr Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint
title_full_unstemmed Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint
title_short Increased chromosomal mobility after DNA damage is controlled by interactions between the recombination machinery and the checkpoint
title_sort increased chromosomal mobility after dna damage is controlled by interactions between the recombination machinery and the checkpoint
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120718/
https://www.ncbi.nlm.nih.gov/pubmed/30181361
http://dx.doi.org/10.1101/gad.317966.118
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