Global analysis of genomic instability caused by DNA replication stress in Saccharomyces cerevisiae.

ABSTRACT: DNA replication stress (DRS)-induced genomic instability is an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability, we measured the rates of genomic alterations throughout the genome in a yeast strain with lowered expression of the replicative DNA polymerase δ. By a genetic test, we showed that most recombinogenic DNA lesions were introduced during S or G₂ phase, presumably as a consequence of broken replication forks. We observed a high rate of chromosome loss, likely reflecting a reduced capacity of the low-polymerase strains to repair double-stranded DNA breaks (DSBs). We also observed a high frequency of deletion events within tandemly repeated genes such as the ribosomal RNA genes. By whole-genome sequencing, we fo

SUBMITTER: Zheng DQ 

PROVIDER: S-EPMC5167146 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature