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Ribonucleotide incorporation by human DNA polymerase ? impacts translesion synthesis and RNase H2 activity.


ABSTRACT: Ribonucleotides (rNs) incorporated in the genome by DNA polymerases (Pols) are removed by RNase H2. Cytidine and guanosine preferentially accumulate over the other rNs. Here we show that human Pol ? can incorporate cytidine monophosphate (rCMP) opposite guanine, 8-oxo-7,8-dihydroguanine, 8-methyl-2?-deoxyguanosine and a cisplatin intrastrand guanine crosslink (cis-PtGG), while it cannot bypass a 3-methylcytidine or an abasic site with rNs as substrates. Pol ? is also capable of synthesizing polyribonucleotide chains, and its activity is enhanced by its auxiliary factor DNA Pol ? interacting protein 2 (PolDIP2). Human RNase H2 removes cytidine and guanosine less efficiently than the other rNs and incorporation of rCMP opposite DNA lesions further reduces the efficiency of RNase H2. Experiments with XP-V cell extracts indicate Pol ? as the major basis of rCMP incorporation opposite cis-PtGG. These results suggest that translesion synthesis by Pol ? can contribute to the accumulation of rCMP in the genome, particularly opposite modified guanines.

SUBMITTER: Mentegari E 

PROVIDER: S-EPMC5389505 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Ribonucleotide incorporation by human DNA polymerase η impacts translesion synthesis and RNase H2 activity.

Mentegari Elisa E   Crespan Emmanuele E   Bavagnoli Laura L   Kissova Miroslava M   Bertoletti Federica F   Sabbioneda Simone S   Imhof Ralph R   Sturla Shana J SJ   Nilforoushan Arman A   Hübscher Ulrich U   van Loon Barbara B   Maga Giovanni G  

Nucleic acids research 20170301 5


Ribonucleotides (rNs) incorporated in the genome by DNA polymerases (Pols) are removed by RNase H2. Cytidine and guanosine preferentially accumulate over the other rNs. Here we show that human Pol η can incorporate cytidine monophosphate (rCMP) opposite guanine, 8-oxo-7,8-dihydroguanine, 8-methyl-2΄-deoxyguanosine and a cisplatin intrastrand guanine crosslink (cis-PtGG), while it cannot bypass a 3-methylcytidine or an abasic site with rNs as substrates. Pol η is also capable of synthesizing poly  ...[more]

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