Impact of 1,N ⁶-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair.

ABSTRACT: Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N ⁶-ethenoadenosine (1,N ⁶-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2-mediated incision. Mass spectral analysis revealed that 1,N ⁶-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e.<

SUBMITTER: Ghodke PP 

PROVIDER: S-EPMC7196658 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature