Abstract
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.