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 journalArticle

103 Citations (Scopus)

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
Pages (from-to)1630-1638
Number of pages9
JournalNucleic Acids Research
Volume30
Issue number7
StatePublished - Apr 1 2002
Externally publishedYes

Fingerprint

Human Activities
DNA Damage
DNA-Directed DNA Polymerase
Benzo(a)pyrene
Guanine
Exonucleases
DNA
Mutagenesis
Nucleotides
fluorene

ASJC Scopus subject areas

  • Genetics

Cite this

Zhang, Y., Wu, X., Rechkoblit, O., Geacintov, N. E., Taylor, J. S., & Wang, Z. (2002). Response of human REV1 to different DNA damage: Preferential dCMP insertion opposite the lesion. Nucleic Acids Research, 30(7), 1630-1638.

Response of human REV1 to different DNA damage : Preferential dCMP insertion opposite the lesion. / Zhang, Yanbin; Wu, Xiaohua; Rechkoblit, Olga; Geacintov, Nicholas E.; Taylor, John Stephen; Wang, Zhigang.

In: Nucleic Acids Research, Vol. 30, No. 7, 01.04.2002, p. 1630-1638.

Research output: Contribution to journalArticle

Zhang, Y, Wu, X, Rechkoblit, O, Geacintov, NE, Taylor, JS & Wang, Z 2002, 'Response of human REV1 to different DNA damage: Preferential dCMP insertion opposite the lesion', Nucleic Acids Research, vol. 30, no. 7, pp. 1630-1638.
Zhang Y, Wu X, Rechkoblit O, Geacintov NE, Taylor JS, Wang Z. Response of human REV1 to different DNA damage: Preferential dCMP insertion opposite the lesion. Nucleic Acids Research. 2002 Apr 1;30(7):1630-1638.
Zhang, Yanbin ; Wu, Xiaohua ; Rechkoblit, Olga ; Geacintov, Nicholas E. ; Taylor, John Stephen ; Wang, Zhigang. / Response of human REV1 to different DNA damage : Preferential dCMP insertion opposite the lesion. In: Nucleic Acids Research. 2002 ; Vol. 30, No. 7. pp. 1630-1638.
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