Translesion replication of benzo[a]pyrene and benzo[c]phenantherene diol epoxide adducts of deoxyadenosine and deoxyguanosine by human DNA polymerase ι

Ekaterina G. Frank, Jane M. Sayer, Heiko Kroth, Eiji Ohashi, Haruo Ohmori, Donald M. Jerina, Roger Woodgate

研究成果: Contribution to journalReview article査読

65 被引用数 (Scopus)

抄録

Human DNA polymerase ι (polι) is a Y-family polymerase whose cellular function is presently unknown. Here, we report on the ability of polι to bypass various stereoisomers of benzo[a]pyrene (BaP) diol epoxide (DE) and benzo[c]phenanthrene (BcPh) DE adducts at deoxyadenosine (dA) or deoxyguanosine (dG) bases in four different template sequence contexts in vitro. We find that the BaP DE dG adducts pose a strong block to polι-dependent replication and result in a high frequency of base misincorporations. In contrast, misincorporations opposite BaP DE and BcPh DE dA adducts generally occurred with a frequency ranging between 2 × 10-3 and 6 × 10-4. Although dTMP was inserted efficiently opposite all dA adducts, further extension was relatively poor, with one exception (a cis opened adduct derived from BcPh DE) where up to 58% extension past the lesion was observed. Interestingly, another human Y-family polymerase, polκ, was able to extend dTMP inserted opposite a BaP DE dA adduct. We suggest that polι might therefore participate in the error-free bypass of DE-adducted dA in vivo by predominantly incorporating dTMP opposite the damaged base. In many cases, elongation would, however, require the participation of another polymerase more specialized in extension, such as polκ.

本文言語英語
ページ(範囲)5284-5292
ページ数9
ジャーナルNucleic acids research
30
23
DOI
出版ステータス出版済み - 12 1 2002
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学

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