The roles of polymerases ν and θ in replicative bypass of O6- And N2-alkyl-2'-deoxyguanosine lesions in human cells

Hua Du, Pengcheng Wang, Jun Wu, Xiaomei He, Yinsheng Wang, Patrick Sung

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Exogenous and endogenous chemicals can react with DNA to produce DNA lesions that may block DNA replication. Not much is known about the roles of polymerase (Pol) ν and Pol θ in translesion synthesis (TLS) in cells. Here we examined the functions of these two polymerases in bypassing major-groove O6-alkyl-2'-deoxyguanosine (O6-alkyl-dG) and minor-groove N2-alkyl-dG lesions in human cells, where the alkyl groups are ethyl, n-butyl (nBu), and, for O6-alkyl-dG, pyridyloxobutyl. We found that Pol ν and Pol θ promote TLS across major-groove O6-alkyl-dG lesions. O6-alkyl-dG lesions mainly induced G3 A mutations that were modulated by the two TLS polymerases and the structures of the alkyl groups. Simultaneous ablation of Pol ν and Pol θ resulted in diminished mutation frequencies for all three O6-alkyl-dG lesions. Depletion of Pol ν alone reduced mutations only for O6-nBu-dG, and sole loss of Pol θ attenuated the mutation rates for O6-nBu-dG and O6-pyridyloxobutyl-dG. Replication across the two N2-alkyl-dG lesions was error-free, and Pol ν and Pol θ were dispensable for their replicative bypass. Together, our results provide critical knowledge about the involvement of Pol ν and Pol θ in bypassing alkylated guanine lesions in human cells.

Original languageEnglish (US)
Pages (from-to)4556-4562
Number of pages7
JournalJournal of Biological Chemistry
Volume295
Issue number14
DOIs
StatePublished - Apr 3 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The roles of polymerases ν and θ in replicative bypass of O<sup>6</sup>- And N<sup>2</sup>-alkyl-2'-deoxyguanosine lesions in human cells'. Together they form a unique fingerprint.

Cite this