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PMID: 11239458 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest.

Molecular cell ·Vol. 7 ·No. 2 ·2001-02-00 ·Pages 293-300

Pellicioli A, Lee SE, Lucca C, Foiani M, Haber JE

Abstract

Saccharomyces cells with one unrepaired double-strand break (DSB) adapt after checkpoint-mediated G2/M arrest. Adaptation is accompanied by loss of Rad53p checkpoint kinase activity and Chk1p phosphorylation. Rad53p kinase remains elevated in yku70delta and cdc5-ad cells that fail to adapt. Permanent G2/M arrest in cells with increased single-stranded DNA is suppressed by the rfa1-t11 mutation, but this RPA mutation does not suppress permanent arrest in cdc5-ad cells. Checkpoint kinase activation and inactivation can be followed in G2-arrested cells, but there is no kinase activation in G1-arrested cells. We conclude that activation of the checkpoint kinases in response to a single DNA break is cell cycle regulated and that adaptation is an active process by which these kinases are inactivated.

MeSH Terms
Adaptation, Biological/genetics Anaphase Antigens, Nuclear Cell Cycle Cell Cycle Proteins/genetics,metabolism Checkpoint Kinase 1 Checkpoint Kinase 2 DNA Damage/genetics DNA Helicases DNA, Fungal/metabolism DNA-Binding Proteins/genetics,metabolism Enzyme Activation Fungal Proteins/metabolism G2 Phase Gene Expression Intracellular Signaling Peptides and Proteins Kinetics Ku Autoantigen Mitosis Mutation Nuclear Proteins/genetics,metabolism Phosphorylation Protein Kinases/metabolism Protein Serine-Threonine Kinases RNA-Binding Proteins Recombination, Genetic Replication Protein A Saccharomyces cerevisiae/cytology,enzymology,genetics,metabolism Saccharomyces cerevisiae Proteins Sequence Homology, Nucleic Acid
Chemicals
Antigens, Nuclear CEF1 protein, S cerevisiae Cell Cycle Proteins DNA, Fungal DNA-Binding Proteins Fungal Proteins Intracellular Signaling Peptides and Proteins Nuclear Proteins RNA-Binding Proteins Replication Protein A Saccharomyces cerevisiae Proteins high affinity DNA-binding factor, S cerevisiae Protein Kinases Checkpoint Kinase 2 Checkpoint Kinase 1 MEC1 protein, S cerevisiae Protein Serine-Threonine Kinases RAD53 protein, S cerevisiae DNA Helicases XRCC5 protein, human Xrcc6 protein, human Ku Autoantigen
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pellicioli A
Istituto F.I.R.C. di Oncologia Molecolare and, Dipartimento di Genetica e di Biologia dei, Microrganismi, Universita' degli Studi di Milano, 20133, Milan, Italy.
Lee S E
Lucca C
Foiani M
Haber J E
Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
Published
2001-02-00
Pages
293-300
Language
English
Region
United States
NLM ID
9802571
Subset
IM
Grants
NIGMS NIH HHS · GM20056 · United States
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