Back to Search
Start Over
Mechanisms involved in regulating DNA replication origins during the cell cycle and in response to DNA damage
- Publication Year :
- 2004
-
Abstract
- Replication origins in eukaryotic cells never fire more than once in a given S phase. Here, we summarize the role of cyclin–dependent kinases in limiting DNA replication origin usage to once per cell cycle in the budding yeastSaccharomyces cerevisiae. We have examined the role of different cyclins in the phosphorylation and regulation of several replication/regulatory factors including Cdc6, Sic1, ORC and DNA polymerase α–primase. In addition to being regulated by the cell cycle machinery, replication origins are also regulated by the genome integrity checkpoint kinases, Mec1 and Rad53. In response to DNA damage or drugs which interfere with the progression of replication forks, the activation of late–firing replication origins is inhibited. There is evidence indicating that the temporal programme of origin firing depends upon the local histone acetylation state. We have attempted to test the possibility that checkpoint regulation of late–origin firing operates through the regulation of the acetylation state. We found that overexpression of the essential histone acetylase, Esa1, cannot override checkpoint regulation of origin firing. We have also constructed a temperature–sensitiveesa1mutant. This mutant is unable to resume cell cycle progression after α–factor arrest. This can be overcome by overexpression of the G1 cyclin, Cln2, revealing a novel role for Esa1 in regulating Start.
- Subjects :
- DNA re-replication
DNA Replication
Saccharomyces cerevisiae Proteins
Eukaryotic DNA replication
Cell Cycle Proteins
Replication Origin
Saccharomyces cerevisiae
Biology
Protein Serine-Threonine Kinases
Pre-replication complex
General Biochemistry, Genetics and Molecular Biology
Histones
Control of chromosome duplication
Acetyltransferases
S phase
Histone Acetyltransferases
Genetics
Cell Cycle
Intracellular Signaling Peptides and Proteins
G2-M DNA damage checkpoint
DNA replication origin
Cyclin-Dependent Kinases
Cell biology
Checkpoint Kinase 2
Origin recognition complex
General Agricultural and Biological Sciences
Research Article
DNA Damage
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b675d5d584cfded6d65bd7d37e298316