Effects of sequence contexts on misincorporation of nucleotides opposite 2‐hydroxyadenine

FEBS Letters

Kasai, Hiroshi¹  Kamiya, Hiroyuki¹ 

[1] Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807, Japan

关键词: 2-Hydroxyadenine;    Oxidative DNA damage;    Misincorporation;    DNA polymerase;    Sequence context;    2-OH-Ade;    2-hydroxyadenine;    2-OH-dAMP;    2-hydroxy-2′-deoxyadenosine 5′-monophosphate;    2-OH-dATP;    2-hydroxy-2′-deoxyadenosine 5′-triphosphate;    8-OH-Gua;    8-hydroxyguanine;    pol α;    DNA polymerase α;    pol β;    DNA polymerase β;    KFexo−;    exonuclease-deficient Klenow fragment of DNA polymerase I;    KFexo+;    exonuclease-proficient Klenow fragment of DNA polymerase I;    dNTP;    2′-deoxynucleoside 5′-triphosphate;   

DOI  :  10.1016/0014-5793(96)00714-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Twelve oligonucleotides containing 2-hydroxyadenine (2-OH-Ade) with different neighboring bases were used as templates in DNA polymerase reactions, and the effects of the sequence contexts were investigated. DNA polymerases α and β inserted dTMP and dCMP opposite 2-OH-Ade in most of the oligonucleotides tested. The Klenow fragment of DNA polymerase I primarily incorporated dTMP and dGMP. Effects of the 5′-flanking base of 2-OH-Ade was found when the 3′-flanking base of 2-OH-Ade was A or C. Incorporation of dAMP occurred when the oxidized base was located in a 5′ -TA^∗A- 3′ (A^∗ represents 2-OH-Ade) sequence. These results suggest that the formation of 2-OH-Ade in DNA may induce all the mutations involving A (A → G transition, and A → T and A → C transversions) in cells.

【 授权许可】

Unknown