Abstract：
:Intrastrand cross-links (IaCL) connecting two purine nucleobases in DNA pose a challenge to high-fidelity replication in the cell. Various repair pathways or polymerase bypass can cope with these lesions. The influence of the phosphodiester linkage between two neighboring 2'-deoxyguanosine (dG) residues attached through the O(6) atoms by an alkylene linker on bypass with human DNA polymerase η (hPol η) was explored in vitro. Steady-state kinetics and mass spectrometric analysis of products from nucleotide incorporation revealed that although hPol η is capable of bypassing the 3'-dG in a mostly error-free fashion, significant misinsertion was observed for the 5'-dG of the IaCL containing a butylene or heptylene linker. The lack of the phosphodiester linkage triggered an important increase in frameshift adduct formation across the 5'-dG by hPol η, in comparison to the 5'-dG of IaCL DNA containing the phosphodiester group.
journal_name
Biochemistryjournal_title
Biochemistryauthors
O'Flaherty DK,Guengerich FP,Egli M,Wilds CJdoi
10.1021/acs.biochem.5b01078subject
Has Abstractpub_date
2015-12-29 00:00:00pages
7449-56issue
51eissn
0006-2960issn
1520-4995journal_volume
54pub_type
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