Response of human DNA polymerase ι to DNA lesions

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Abstract

Lesion bypass is an important mechanism to overcome replication blockage by DNA damage. Translesion synthesis requires a DNA polymerase (Pol). Human Pol ι encoded by the RAD30B gene is a recently identified DNA polymerase that shares sequence similarity to Pol η. To investigate whether human Pol ι plays a role in lesion bypass we examined the response of this polymerase to several types of DNA damage in vitro. Surprisingly, 8-oxoguanine significantly blocked human Pol ι. Nevertheless, translesion DNA synthesis opposite 8-oxoguanine was observed with increasing concentrations of purified human Pol ι, resulting in predominant C and less frequent A incorporation opposite the lesion. Opposite a template abasic site human Pol ι efficiently incorporated a G, less frequently a T and even less frequently an A. Opposite an AAF-adducted guanine, human Pol ι was able to incorporate predominantly a C. In both cases, however, further DNA synthesis was not observed. Purified human Pol ι responded to a template TT (6-4) photoproduct by inserting predominantly an A opposite the 3′ T of the lesion before aborting DNA synthesis. In contrast, human Pol ι was largely unresponsive to a template TT cis-syn cyclobutane dimer. These results suggest a role for human Pol ι in DNA lesion bypass.

Original languageEnglish
Pages (from-to)928-935
Number of pages8
JournalNucleic Acids Research
Volume29
Issue number4
StatePublished - Feb 15 2001
Externally publishedYes

Cite this

Response of human DNA polymerase ι to DNA lesions. / Zhang, Yanbin; Yuan, Fenghua; Wu, Xiaohua; Taylor, John Stephen; Wang, Zhigang.

In: Nucleic Acids Research, Vol. 29, No. 4, 15.02.2001, p. 928-935.

Research output: Contribution to journalArticle