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Phosphorylation of Rad55 on serines 2, 8, and 14 is required for efficient homologous recombination in the recovery of stalled replication forks.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2006 Nov; Vol. 26 (22), pp. 8396-409. Date of Electronic Publication: 2006 Sep 11. - Publication Year :
- 2006
-
Abstract
- DNA damage checkpoints coordinate the cellular response to genotoxic stress and arrest the cell cycle in response to DNA damage and replication fork stalling. Homologous recombination is a ubiquitous pathway for the repair of DNA double-stranded breaks and other checkpoint-inducing lesions. Moreover, homologous recombination is involved in postreplicative tolerance of DNA damage and the recovery of DNA replication after replication fork stalling. Here, we show that the phosphorylation on serines 2, 8, and 14 (S2,8,14) of the Rad55 protein is specifically required for survival as well as for normal growth under genome-wide genotoxic stress. Rad55 is a Rad51 paralog in Saccharomyces cerevisiae and functions in the assembly of the Rad51 filament, a central intermediate in recombinational DNA repair. Phosphorylation-defective rad55-S2,8,14A mutants display a very slow traversal of S phase under DNA-damaging conditions, which is likely due to the slower recovery of stalled replication forks or the slower repair of replication-associated DNA damage. These results suggest that Rad55-S2,8,14 phosphorylation activates recombinational repair, allowing for faster recovery after genotoxic stress.
- Subjects :
- Adenosine Triphosphatases
Amino Acid Sequence
Cell Cycle Proteins metabolism
Checkpoint Kinase 2
DNA Repair
DNA Repair Enzymes
DNA Replication
DNA-Binding Proteins genetics
Genome
Mass Spectrometry
Models, Genetic
Molecular Sequence Data
Phosphorylation
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins c-raf metabolism
Rad52 DNA Repair and Recombination Protein metabolism
Saccharomyces cerevisiae Proteins genetics
Serine
DNA Damage
DNA, Fungal
DNA-Binding Proteins metabolism
Gene Expression Regulation, Fungal
Recombination, Genetic
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 26
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16966380
- Full Text :
- https://doi.org/10.1128/MCB.01317-06