Open AccessDamage Tolerance Protein Mus81 Associates with the FHA1 Domain of Checkpoint Kinase Cds1
Author(s) -
Michael N. Boddy,
Antonia López-Girona,
Paul Shanahan,
Heidrun Interthal,
WolfDietrich Heyer,
Paul Russell
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.23.8758-8766.2000
Subject(s) - biology , g2 m dna damage checkpoint , schizosaccharomyces pombe , genetics , dna repair , chek1 , cell cycle checkpoint , schizosaccharomyces , microbiology and biotechnology , anaphase promoting complex , nucleotide excision repair , homologous recombination , helicase , cell cycle , dna , gene , saccharomyces cerevisiae , rna
Cds1, a serine/threonine kinase, enforces the S-M checkpoint in the fission yeastSchizosaccharomyces pombe . Cds1 is required for survival of replicational stress caused by agents that stall replication forks, but how Cds1 performs these functions is largely unknown. Here we report that the forkhead-associated-1 (FHA1) protein-docking domain of Cds1 interacts with Mus81, an evolutionarily conserved damage tolerance protein. Mus81 has an endonuclease homology domain found in the XPF nucleotide excision repair protein. Inactivation ofmus81 reveals a unique spectrum of phenotypes. Mus81 enables survival of deoxynucleotide triphosphate starvation, UV radiation, and DNA polymerase impairment. Mus81 is essential in the absence of Bloom's syndrome Rqh1 helicase and is required for productive meiosis. Genetic epistasis studies suggest that Mus81 works with recombination enzymes to properly replicate damaged DNA. Inactivation of Mus81 triggers a checkpoint-dependent delay of mitosis. We propose that Mus81 is involved in the recruitment of Cds1 to aberrant DNA structures where Cds1 modulates the activity of damage tolerance enzymes.