Mutation signatures reveal the role of RAD52 recombinase in fueling genome instability and escape from senescence

Genomic instability shapes the cancer genome providing a decisive selection process that promotes malignancy.

Extending on a previous study we show that chronic p53-independent p21 WAF1/Cip1 expression can fuel genomic instability, bypassing the antitumor barrier of senescence, not only by deregulating the replication licensing machinery but by suppressing the activity of the translesion DNA synthesis and repair (TLS) pathway, as well. Scrutinizing the mutation signatures of the cells that “escaped” senescence we discovered that Rad52-dependent Break-Induced Replication (BIR) and Single Strand Annealing (SSA) represent the main origin of p21 WAF1/Cip1 – mediated genomic instability. We suggest and pinpoint Rad52 as a promising therapeutic target when most other error-free repair players are defected.

Source: https://www.irbbarcelona.org/en/events/mutation-signatures-reveal-the-role-of-rad52-recombinase-in-fueling-genome-instability-and

VG New

Prof. Vassilis G. Gorgoulis

Laboratory of Histology-Embryology
Molecular Carcinogenesis Group
Medical School
National and Kapodistrian University of Athens

 

Biomedical Research Foundation of the Academy of Athens

 

Faculty Institute for Cancer Sciences, University of Manchester,
Manchester Academic Health Science Centre, Manchester, UK

Manchester Centre for Cellular Metabolism,
University of Manchester, Manchester Academic Health Science Centre, Manchester

 

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