RRC ID 35765
著者 Saka Y, Esashi F, Matsusaka T, Mochida S, Yanagida M.
タイトル Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1.
ジャーナル Genes Dev
Abstract Fission yeast Cut5/Rad4 plays a unique role in the genome maintenance as it is required for replication, replication checkpoint, and normal UV sensitivity. It is unknown, however, how Cut5 protein is linked to other checkpoint proteins, and what part it plays in replication and UV sensitivity. Here we report that Cut5 interacts with a novel checkpoint protein Crb2 and that this interaction is needed for normal genome maintenance. The carboxyl terminus of Crb2 resembles yeast Rad9 and human 53BP1 and BRCA1. Crb2 is required for checkpoint arrests induced by irradiation and polymerase mutations, but not for those induced by inhibited nucleotide supply. Upon UV damage, Crb2 is transiently modified, probably phosphorylated, with a similar timing of phosphorylation in Chk1 kinase, which is reported to restrain Cdc2 activation. Crb2 modification requires other damage-sensing checkpoint proteins but not Chk1, suggesting that Crb2 acts at the upstream of Chk1. The modified Crb2 exists as a slowly sedimenting form, whereas Crb2 in undamaged cells is in a rapidly sedimenting structure. Cut5 and Crb2 interact with Chk1 in a two-hybrid system. Moreover, moderate overexpression of Chk1 suppresses the phenotypes of cut5 and crb2 mutants. Cut5, Crb2, and Chk1 thus may form a checkpoint sensor-transmitter pathway to arrest the cell cycle.
巻・号 11(24)
ページ 3387-400
公開日 1997-12-15
DOI 10.1101/gad.11.24.3387
PMID 9407031
PMC PMC316798
MeSH Amino Acid Sequence BRCA1 Protein / genetics Binding Sites Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Checkpoint Kinase 1 Conserved Sequence DNA Damage / genetics DNA Damage / radiation effects DNA Replication / genetics DNA-Binding Proteins* DNA-Directed DNA Polymerase / genetics Fungal Proteins / genetics Fungal Proteins / metabolism* Fungal Proteins / radiation effects Genes, Fungal Hydroxyurea / pharmacology Molecular Sequence Data Mutation Nuclear Proteins / genetics Nuclear Proteins / metabolism* Protein Kinases / genetics Protein Kinases / metabolism* Repetitive Sequences, Nucleic Acid Schizosaccharomyces / drug effects Schizosaccharomyces / genetics* Schizosaccharomyces / radiation effects Schizosaccharomyces pombe Proteins* Sequence Homology, Amino Acid Transglutaminases* Ultraviolet Rays
IF 9.527
引用数 221
WOS 分野 GENETICS & HEREDITY CELL BIOLOGY DEVELOPMENTAL BIOLOGY
リソース情報
遺伝子材料 chk1+ (RDB02949) crb2+ (RDB02950).