Ribonucleotide incorporation by human DNA polymerase eta impacts translesion synthesis and RNase H2 activity
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Date
2017-03-17
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Journal Article
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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 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 polyribonucleotide chains, and its activity is enhanced by its auxiliary factor DNA Pol δ 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 η as the major basis of rCMP incorporation opposite cis-PtGG. These results suggest that translesion synthesis by Pol η can contribute to the accumulation of rCMP in the genome, particularly opposite modified guanines.
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published
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Journal / series
Volume
45 (5)
Pages / Article No.
2600 - 2614
Publisher
Oxford University Press
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Organisational unit
03853 - Sturla, Shana / Sturla, Shana
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Funding
156280 - DNA Alkylation and Resistance in Antitumor Drug Toxicity (SNF)