Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.

Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bif...

Full description

Bibliographic Details
Main Authors: Jennifer S Searle, Matthew D Wood, Mandeep Kaur, David V Tobin, Yolanda Sanchez
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-07-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC3136438?pdf=render
id doaj-bc4ac509943a4ca8923e39617b471ddc
record_format Article
spelling doaj-bc4ac509943a4ca8923e39617b471ddc2020-11-25T00:07:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-07-0177e100217610.1371/journal.pgen.1002176Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.Jennifer S SearleMatthew D WoodMandeep KaurDavid V TobinYolanda SanchezCheckpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate both the metaphase to anaphase transition and mitotic exit. The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network. We have previously shown that the PKA pathway plays a role in blocking securin and Clb2 destruction following DNA damage. Here we show that the Mec1 DNA damage checkpoint regulates phosphorylation of the regulatory (R) subunit of PKA following DNA damage and that the phosphorylated R subunit has a role in restraining mitosis following DNA damage. In addition we found that proteins known to regulate PKA in response to nutrients and stress either by phosphorylation of the R subunit or regulating levels of cAMP are required for the role of PKA in the DNA damage checkpoint. Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA.http://europepmc.org/articles/PMC3136438?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Jennifer S Searle
Matthew D Wood
Mandeep Kaur
David V Tobin
Yolanda Sanchez
spellingShingle Jennifer S Searle
Matthew D Wood
Mandeep Kaur
David V Tobin
Yolanda Sanchez
Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.
PLoS Genetics
author_facet Jennifer S Searle
Matthew D Wood
Mandeep Kaur
David V Tobin
Yolanda Sanchez
author_sort Jennifer S Searle
title Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.
title_short Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.
title_full Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.
title_fullStr Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.
title_full_unstemmed Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.
title_sort proteins in the nutrient-sensing and dna damage checkpoint pathways cooperate to restrain mitotic progression following dna damage.
publisher Public Library of Science (PLoS)
series PLoS Genetics
issn 1553-7390
1553-7404
publishDate 2011-07-01
description Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate both the metaphase to anaphase transition and mitotic exit. The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network. We have previously shown that the PKA pathway plays a role in blocking securin and Clb2 destruction following DNA damage. Here we show that the Mec1 DNA damage checkpoint regulates phosphorylation of the regulatory (R) subunit of PKA following DNA damage and that the phosphorylated R subunit has a role in restraining mitosis following DNA damage. In addition we found that proteins known to regulate PKA in response to nutrients and stress either by phosphorylation of the R subunit or regulating levels of cAMP are required for the role of PKA in the DNA damage checkpoint. Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA.
url http://europepmc.org/articles/PMC3136438?pdf=render
work_keys_str_mv AT jenniferssearle proteinsinthenutrientsensinganddnadamagecheckpointpathwayscooperatetorestrainmitoticprogressionfollowingdnadamage
AT matthewdwood proteinsinthenutrientsensinganddnadamagecheckpointpathwayscooperatetorestrainmitoticprogressionfollowingdnadamage
AT mandeepkaur proteinsinthenutrientsensinganddnadamagecheckpointpathwayscooperatetorestrainmitoticprogressionfollowingdnadamage
AT davidvtobin proteinsinthenutrientsensinganddnadamagecheckpointpathwayscooperatetorestrainmitoticprogressionfollowingdnadamage
AT yolandasanchez proteinsinthenutrientsensinganddnadamagecheckpointpathwayscooperatetorestrainmitoticprogressionfollowingdnadamage
_version_ 1725418293279326208