Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage.
Saccharomyces cells suffering a single unrepairable double-strand break (DSB) exhibit a long, but transient arrest at G2/M. hdf1 cells, lacking Ku70p, fail to escape from this RAD9/RAD17-dependent checkpoint. The effect of hdf1 results from its accelerated 5' to 3' degradation of the broken chromosome. Permanent arrest in hdf1 cells is suppressed by rad50 or mre11 deletions that retard this degradation. Wild-type HDF1 cells also become permanently arrested when they experience two unrepairable DSBs. Both DSB-induced arrest conditions are suppressed by a mutation in the single-strand binding protein, RPA. We suggest that escape from the DNA damage-induced G2/M checkpoint depends on the extent of ssDNA created at broken chromosome ends. RPA appears to play a key intermediate step in this adaptation.
Lee
S E
SE
Rosenstiel Center, Department of Biology, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Moore
J K
JK
Holmes
A
A
Umezu
K
K
Kolodner
R D
RD
Haber
J E
JE
D000222:Adaptation, Physiological / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics; D004249:DNA Damage / Q000235:genetics* / Q000502:physiology; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins / Q000502:physiology*; D016195:G2 Phase / Q000235:genetics* / Q000502:physiology; D008938:Mitosis / Q000235:genetics* / Q000502:physiology; D051716:Replication Protein A; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C086930:RAD50 protein, S cerevisiae; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; C520769:YKU70 protein, S cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; C037725:SCEI protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific