Base substitution specificity of DNA polymerase β depends on interactions in the DNA minor groove

被引:62
|
作者
Osheroff, WP
Beard, WA
Wilson, SH
Kunkel, TK [1 ]
机构
[1] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA
[2] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1074/jbc.274.30.20749
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To examine the hypothesis that interactions between a DNA polymerase and the DNA minor groove are critical for accurate DNA synthesis, we studied the fidelity of DNA polymerase beta mutants at residue Arg(283), where arginine, which interacts with the minor groove at the active site, is replaced by alanine or lysine. Alanine substitution, removing minor groove interactions, strongly reduces polymerase selectivity for all single-base mispairs examined. In contrast, the lysine substitution, which retains significant interactions with the minor groove, has wild-type-like selectivity for T.dGMP and A.dGMP mispairs but reduced selectivity for T.dCMP and A.dCMP mispairs, Examination of DNA crystal structures of these four mispairs indicates that the two mispairs excluded by the lysine mutant have an atom (N2) in an unfavorable position in the minor groove, while the two mispairs permitted by the lysine mutant do not. These results suggest that unfavorable interactions between an active site amino acid side chain and mispair-specific atoms in the minor groove contribute to DNA polymerase specificity.
引用
收藏
页码:20749 / 20752
页数:4
相关论文
共 50 条
  • [31] Diaminobenzene schiff base, a novel class of DNA minor groove binder
    Helal, Muath H.
    Al-Mudaris, Zena A.
    Al-Douh, Mohammed H.
    Osman, Hasnah
    Wahab, Habibah A.
    Alnajjar, Belal O.
    Abdallah, Hassan H.
    Majid, Amin M. S. Abdul
    INTERNATIONAL JOURNAL OF ONCOLOGY, 2012, 41 (02) : 504 - 510
  • [32] RECOGNITION OF G,C BASE-PAIRS IN THE MINOR GROOVE OF DNA
    WADE, WS
    DERVAN, PB
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1988, 196 : 235 - ORGN
  • [33] Efficient and Accurate Bypass of a Minor-Groove DNA Adduct by DinB DNA Polymerase in Vitro and in Vivo
    Wang, Yinsheng
    Yuan, Bifeng
    Cao, Huachuan
    Jiang, Yong
    Wang, Jianshuang
    CHEMICAL RESEARCH IN TOXICOLOGY, 2008, 21 (12) : 2452 - 2452
  • [34] Yeast DNA polymerase η makes functional contacts with the DNA minor groove only at the incoming nucleoside triphosphate
    Washington, MT
    Wolfle, WT
    Spratt, TE
    Prakash, L
    Prakash, S
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (09) : 5113 - 5118
  • [35] A new type of DNA minor-groove complex: Carbazole dication-DNA interactions
    Tanious, FA
    Ding, DY
    Patrick, DA
    Tidwell, RR
    Wilson, WD
    BIOCHEMISTRY, 1997, 36 (49) : 15315 - 15325
  • [36] ON SPECIFICITY OF DNA POLYMERASE
    FREESE, EB
    FREESE, E
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1967, 57 (03) : 650 - +
  • [38] DNA minor groove binding agents
    Damia, G
    Broggini, M
    DRUGS OF THE FUTURE, 2005, 30 (03) : 301 - 309
  • [40] DNA recognition -: Reading the minor groove
    Hélène, C
    NATURE, 1998, 391 (6666) : 436 - 438