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Erroneous incorporation of oxidized DNA precursors by Y‐family DNA polymerases
Author(s) -
Shimizu Masatomi,
Gruz Petr,
Kamiya Hiroyuki,
Kim SuRyang,
Pisani Francesca M,
Masutani Chikahide,
Kanke Yusuke,
Harashima Hideyoshi,
Hanaoka Fumio,
Nohmi Takehiko
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor765
Subject(s) - dna polymerase , dna polymerase ii , dna clamp , polymerase , primase , dna polymerase mu , dna , dna replication , biology , primer (cosmetics) , biochemistry , dna polymerase i , dna synthesis , sulfolobus solfataricus , microbiology and biotechnology , chemistry , circular bacterial chromosome , polymerase chain reaction , gene , reverse transcriptase , organic chemistry , archaea
Deranged oxidative metabolism is a property of many tumour cells. Oxidation of the deoxynucleotide triphosphate (dNTP) pool, as well as DNA, is a major cause of genome instability. Here, we report that two Y‐family DNA polymerases of the archaeon Sulfolobus solfataricus strains P1 and P2 incorporate oxidized dNTPs into nascent DNA in an erroneous manner: the polymerases exclusively incorporate 8‐OH‐dGTP opposite adenine in the template, and incorporate 2‐OH‐dATP opposite guanine more efficiently than opposite thymine. The rate of extension of the nascent DNA chain following on from these incorporated analogues is only slightly reduced. These DNA polymerases have been shown to bypass a variety of DNA lesions. Thus, our results suggest that the Y‐family DNA polymerases promote mutagenesis through the erroneous incorporation of oxidized dNTPs during DNA synthesis, in addition to facilitating translesion DNA synthesis. We also report that human DNA polymerase η, a human Y‐family DNA polymerase, incorporates the oxidized dNTPs in a similar erroneous manner.

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