Dan Chen, Judit Z Gervai, Ádám Póti, Eszter Németh, Zoltán Szeltner, Bernadett Szikriszt, Zsolt Gyüre, Judit Zámborszky, Marta Ceccon, Fabrizio d'Adda di Fagagna, Zoltan Szallasi, Andrea L Richardson, Dávid Szüts
Defects in BRCA1, BRCA2 and other genes of the homology-dependent DNA repair (HR) pathway cause an elevated rate of mutagenesis, eliciting specific mutation patterns including COSMIC signature SBS3. Using genome sequencing of knock-out cell lines we show that Y family translesion synthesis (TLS) polymerases contribute to the spontaneous generation of base substitution and short insertion/deletion mutations in BRCA1 deficient cells, and that TLS on DNA adducts is increased in BRCA1 and BRCA2 mutants. The inactivation of 53BP1 in BRCA1 mutant cells markedly reduces TLS-specific mutagenesis, and rescues the deficiency of template switch-mediated gene conversions in the immunoglobulin V locus of BRCA1 mutant chicken DT40 cells...
January 11, 2022: Nature Communications