Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability.
Some spontaneous gross chromosomal rearrangements (GCRs) seem to result from DNA-replication errors. The chromatin-assembly factor I (CAF-I) and replication-coupling assembly factor (RCAF) complexes function in chromatin assembly during DNA replication and repair and could play a role in maintaining genome stability. Inactivation of CAF-I or RCAF increased the rate of accumulating different types of GCRs including translocations and deletion of chromosome arms with associated de novo telomere addition. Inactivation of CAF-I seems to cause damage that activates the DNA-damage checkpoints, whereas inactivation of RCAF seems to cause damage that activates the DNA-damage and replication checkpoints. Both defects result in increased genome instability that is normally suppressed by these checkpoints, RAD52-dependent recombination, and PIF1-dependent inhibition of de novo telomere addition. Treatment of CAF-I- or RCAF-defective cells with methyl methanesulfonate increased the induction of GCRs compared with that seen for a wild-type strain. These results indicate that coupling of chromatin assembly to DNA replication and DNA repair is critical to maintaining genome stability.
Myung
Kyungjae
K
Ludwig Institute for Cancer Research, Cancer Center and Department of Medicine, University of California at San Diego School of Medicine, La Jolla 92093, USA.
Pennaneach
Vincent
V
Kats
Ellen S
ES
Kolodner
Richard D
RD
D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins