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

Autori

Mentegari E, Crespan E, Bavagnoli L, Kissova M, Bertoletti F, Sabbioneda S, Imhof R, Sturla SJ, Nilforoushan A, Hubscher U, van Loon B, Maga G.

Riferimenti

Nucleic Acids Research 45(5) 2600-2614, 2017

Autori CNR

CRESPAN, MAGA, SABBIONEDA

Moduli

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 eta is also capable of synthesizing polyribonucleotide chains, and its activity is enhanced by its auxiliary factor DNA Pol delta 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 eta as the major basis of rCMP incorporation opposite cis-PtGG. These results suggest that translesion synthesis by Pol eta can contribute to the accumulation of rCMP in the genome, particularly opposite modified guanines.

Link all articolo

https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw1275

Parole Chiave

Note

doi.org/10.1093/nar/gkw1275

Indietro


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