DNA polymerase θ accomplishes translesion synthesis opposite 1, N 6 -ethenodeoxyadenosine with a remarkably high fidelity in human cells

Jung Hoon Yoon, Robert E. Johnson, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

Abstract

Here we show that translesion synthesis (TLS) opposite 1, N 6 -ethenodeoxyadenosine (εdA), which disrupts Watson– Crick base pairing, occurs via Polι/Polζ-, Rev1-, and Polθ-dependent pathways. The requirement of Polι/Polζ is consistent with the ability of Polι to incorporate nucleotide opposite εdA by Hoogsteen base pairing and of Polζ to extend synthesis. Rev1 polymerase and Polθ conduct TLS opposite εdA via alternative error-prone pathways. Strikingly, in contrast to extremely error-prone TLS opposite εdA by purified Polθ, it performs predominantly error-free TLS in human cells. Reconfiguration of the active site opposite εdA would provide Polθ the proficiency for error-free TLS in human cells.

Original languageEnglish (US)
Pages (from-to)282-287
Number of pages6
JournalGenes and Development
Volume33
Issue number5-6
DOIs
StatePublished - Mar 1 2019

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DNA-Directed DNA Polymerase
Base Pairing
Catalytic Domain
Nucleotides
1,N(6)-ethenodeoxyadenosine

Keywords

  • DNA polymerase θ
  • Hoogsteen base pairing
  • Translesion synthesis
  • εdA lesion

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

DNA polymerase θ accomplishes translesion synthesis opposite 1, N 6 -ethenodeoxyadenosine with a remarkably high fidelity in human cells . / Yoon, Jung Hoon; Johnson, Robert E.; Prakash, Louise; Prakash, Satya.

In: Genes and Development, Vol. 33, No. 5-6, 01.03.2019, p. 282-287.

Research output: Contribution to journalArticle

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