Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability.

ABSTRACT:

Background

Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design of appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property of p21^WAF1/Cip1, showing that its chronic expression in a p53-deficient environment causes genomic instability by deregulation of the replication licensing machinery.

Results

We now demonstrate that p21^WAF1/Cip1 can further fuel genomic instability by suppressing the repair capacity of low- and high-fidelity pathways that deal with nucleotide abnormalities. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting

SUBMITTER: Galanos P 

PROVIDER: S-EPMC5857109 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature