Publikationsdatum:
1999-11-05
Beschreibung:
In response to DNA damage, cells activate checkpoint pathways that prevent cell cycle progression. In fission yeast and mammals, mitotic arrest in response to DNA damage requires inhibitory Cdk phosphorylation regulated by Chk1. This study indicates that Chk1 is required for function of the DNA damage checkpoint in Saccharomyces cerevisiae but acts through a distinct mechanism maintaining the abundance of Pds1, an anaphase inhibitor. Unlike other checkpoint mutants, chk1 mutants were only mildly sensitive to DNA damage, indicating that checkpoint functions besides cell cycle arrest influence damage sensitivity. Another kinase, Rad53, was required to both maintain active cyclin-dependent kinase 1, Cdk1(Cdc28), and prevent anaphase entry after checkpoint activation. Evidence suggests that Rad53 exerts its role in checkpoint control through regulation of the Polo kinase Cdc5. These results support a model in which Chk1 and Rad53 function in parallel through Pds1 and Cdc5, respectively, to prevent anaphase entry and mitotic exit after DNA damage. This model provides a possible explanation for the role of Cdc5 in DNA damage checkpoint adaptation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanchez, Y -- Bachant, J -- Wang, H -- Hu, F -- Liu, D -- Tetzlaff, M -- Elledge, S J -- GM44664/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1166-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550056" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Anaphase
;
Anaphase-Promoting Complex-Cyclosome
;
CDC2 Protein Kinase/metabolism
;
Cell Cycle Proteins/genetics/metabolism
;
Checkpoint Kinase 2
;
Cyclin B/genetics/metabolism
;
*DNA Damage
;
DNA, Fungal/metabolism
;
Fungal Proteins/genetics/metabolism
;
Intracellular Signaling Peptides and Proteins
;
Ligases/metabolism
;
*Mitosis
;
Mutation
;
Nuclear Proteins/metabolism
;
Phosphorylation
;
Protein Kinases/genetics/*metabolism
;
*Protein-Serine-Threonine Kinases
;
RNA-Binding Proteins
;
Recombinant Fusion Proteins/metabolism
;
S Phase
;
Saccharomyces cerevisiae/*cytology/*enzymology/genetics
;
*Saccharomyces cerevisiae Proteins
;
Securin
;
*Ubiquitin-Protein Ligase Complexes
;
Ubiquitin-Protein Ligases
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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