Response of human REV1 to different DNA damage: Preferential dCMP insertion opposite the lesion

Yanbin Zhang, Xiaohua Wu, Olga Rechkoblit, Nicholas E. Geacintov, John Stephen Taylor, Zhigang Wang

Research output: Contribution to journalReview articlepeer-review

108 Scopus citations

Abstract

REV1 functions in the DNA polymerase ζ mutagenesis pathway. To help understand the role of REV1 in lesion bypass, we have examined activities of purified human REV1 opposite various template bases and several different DNA lesions. Lacking a 3′→5′ proofreading exonuclease activity, purified human REV1 exhibited a DNA polymerase activity on a repeating template G sequence, but catalyzed nucleotide insertion with 6-fold lower efficiency opposite a template A and 19-27-fold lower efficiency opposite a template T or C. Furthermore, dCMP insertion was greatly preferred regardless of the specific template base. Human REV1 inserted a dCMP efficiently opposite a template 8-oxoguanine, (+)-trans-anti-benzo[a]pyrene-N2-dG, (-)-trans-anti-benzo[a]pyrene-N2-dG and 1,N6-ethenoadenine adducts, very inefficiently opposite an acetylamino-fluorene-adducted guanine, but was unresponsive to fluorene-adducted guanine, but was unresponsive to a template TT dimer or TT (6-4) photoproduct. Surprisingly, the REV1 specificity of nucleotide insertion was very similar in response to different DNA lesions with greatly preffered C insertion and least frequent A insertion. By combining the dCMP insertion activity of human REV1 with the extension synthesis activity of human polymerase κ, bypass of the trans-anti-benzo[a]pyrene-N2-dG adducts and the 1,N6-ethenoadenine lesion was achieved by the two-polymerase two-step mechanism. These results suggest that human REV1 is a specialized DNA polymerase that may contribute to dCMP insertion opposite many types of DNA damage during lesion bypass.

Original languageEnglish (US)
Pages (from-to)1630-1638
Number of pages9
JournalNucleic acids research
Volume30
Issue number7
DOIs
StatePublished - Apr 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Response of human REV1 to different DNA damage: Preferential dCMP insertion opposite the lesion'. Together they form a unique fingerprint.

Cite this