Cargando…
Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae
We studied the function of the cyclin-dependent kinase Cdc28 (Cdk1) in the DNA damage response and maintenance of genome stability using Saccharomyces cerevisiae. Reduced Cdc28 activity sensitizes cells to chronic DNA damage, but Cdc28 is not required for cell viability upon acute exposure to DNA-da...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700387/ https://www.ncbi.nlm.nih.gov/pubmed/19398760 http://dx.doi.org/10.1083/jcb.200811083 |
_version_ | 1782168602107969536 |
---|---|
author | Enserink, Jorrit M. Hombauer, Hans Huang, Meng-Er Kolodner, Richard D. |
author_facet | Enserink, Jorrit M. Hombauer, Hans Huang, Meng-Er Kolodner, Richard D. |
author_sort | Enserink, Jorrit M. |
collection | PubMed |
description | We studied the function of the cyclin-dependent kinase Cdc28 (Cdk1) in the DNA damage response and maintenance of genome stability using Saccharomyces cerevisiae. Reduced Cdc28 activity sensitizes cells to chronic DNA damage, but Cdc28 is not required for cell viability upon acute exposure to DNA-damaging agents. Cdc28 is also not required for activation of the DNA damage and replication checkpoints. Chemical–genetic analysis reveals that CDC28 functions in an extensive network of pathways involved in maintenance of genome stability, including homologous recombination, sister chromatid cohesion, the spindle checkpoint, postreplication repair, and telomere maintenance. In addition, Cdc28 and Mre11 appear to cooperate to prevent mitotic catastrophe after DNA replication arrest. We show that reduced Cdc28 activity results in suppression of gross chromosomal rearrangements (GCRs), indicating that Cdc28 is required for formation or recovery of GCRs. Thus, we conclude that Cdc28 functions in a genetic network that supports cell viability during DNA damage while promoting the formation of GCRs. |
format | Text |
id | pubmed-2700387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27003872009-11-04 Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae Enserink, Jorrit M. Hombauer, Hans Huang, Meng-Er Kolodner, Richard D. J Cell Biol Research Articles We studied the function of the cyclin-dependent kinase Cdc28 (Cdk1) in the DNA damage response and maintenance of genome stability using Saccharomyces cerevisiae. Reduced Cdc28 activity sensitizes cells to chronic DNA damage, but Cdc28 is not required for cell viability upon acute exposure to DNA-damaging agents. Cdc28 is also not required for activation of the DNA damage and replication checkpoints. Chemical–genetic analysis reveals that CDC28 functions in an extensive network of pathways involved in maintenance of genome stability, including homologous recombination, sister chromatid cohesion, the spindle checkpoint, postreplication repair, and telomere maintenance. In addition, Cdc28 and Mre11 appear to cooperate to prevent mitotic catastrophe after DNA replication arrest. We show that reduced Cdc28 activity results in suppression of gross chromosomal rearrangements (GCRs), indicating that Cdc28 is required for formation or recovery of GCRs. Thus, we conclude that Cdc28 functions in a genetic network that supports cell viability during DNA damage while promoting the formation of GCRs. The Rockefeller University Press 2009-05-04 /pmc/articles/PMC2700387/ /pubmed/19398760 http://dx.doi.org/10.1083/jcb.200811083 Text en © 2009 Enserink 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.jcb.org/misc/terms.shtml). 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 Enserink, Jorrit M. Hombauer, Hans Huang, Meng-Er Kolodner, Richard D. Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae |
title | Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae |
title_full | Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae |
title_fullStr | Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae |
title_full_unstemmed | Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae |
title_short | Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae |
title_sort | cdc28/cdk1 positively and negatively affects genome stability in s. cerevisiae |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700387/ https://www.ncbi.nlm.nih.gov/pubmed/19398760 http://dx.doi.org/10.1083/jcb.200811083 |
work_keys_str_mv | AT enserinkjorritm cdc28cdk1positivelyandnegativelyaffectsgenomestabilityinscerevisiae AT hombauerhans cdc28cdk1positivelyandnegativelyaffectsgenomestabilityinscerevisiae AT huangmenger cdc28cdk1positivelyandnegativelyaffectsgenomestabilityinscerevisiae AT kolodnerrichardd cdc28cdk1positivelyandnegativelyaffectsgenomestabilityinscerevisiae |