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Research Article |
1 Center for Molecular Oncology, University of Chicago, Chicago IL 60637,
USA
2 Department of Molecular Genetics and Cell Biology, University of Chicago,
Chicago IL 60637, USA
Author for correspondence (e-mail: skron{at}midway.uchicago.edu )
Accepted 27 January 2002
Although most eukaryotes can arrest in G1 after ionizing radiation, the
existence or significance of a G1 checkpoint in S. cerevisiae has
been challenged. Previous studies of G1 response to chemical mutagens, X-ray
or UV irradiation indicate that the delay before replication is transient and
may reflect a strong intra-S-phase checkpoint. We examined the yeast response
to double-stranded breaks in G1 using 
irradiation. G1 irradiation
induces repair foci on chromosome spreads and a Rad53 band shift
characteristic of activation, which suggest an active DNA damage response.
Consistent with a G1 arrest, bud emergence, spindle pole duplication and DNA
replication are each delayed in a dose-dependent manner. Sensitivity to mating
pheromone is prolonged to over 18 hours when G1 cells are lethally or
UV irradiated. Strikingly, G1 delay is the predominant response to continuous
irradiation at a dose that confers no loss of viability but delays
cell division. Like the G2/M checkpoint, G1 delay is completely dependent on
both RAD9 and RAD24 epistasis groups but independent of
POL
. Lethally irradiated rad9 mutants rapidly exit G1
but perform a slow S phase, whereas rad17 and rad24 mutants
are completely arrest deficient. Distinct from irradiation, G1 arrest
after UV is RAD14 dependent, suggesting that DNA damage processing is
required for checkpoint activation. Therefore, as in the yeast G2/M checkpoint
response, free DNA ends and/or single-stranded DNA are necessary and
sufficient to induce a bona fide G1 checkpoint arrest.
Key words: DNA damage checkpoint, DNA repair, G1 phase, Sacchromyces cerevisiae, Genetics, Metabolism, Gamma radiation, Cell cycle, RAD9
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