THE MOLECULAR MECHANISM OF INHIBITION OF ALPHA-TYPE DNA-POLYMERASES BY N2-(BUTYLPHENYL)DGTP AND 2-(BUTYLANILINO)DATP - VARIATION IN SUSCEPTIBILITY TO POLYMERIZATION

被引：16

作者：

KHAN, NN ^{[1
]}

WRIGHT, GE ^{[1
]}

BROWN, NC ^{[1
]}

机构：

[1] UNIV MASSACHUSETTS,SCH MED,DEPT PHARMACOL,WORCESTER,MA 01655

来源：

NUCLEIC ACIDS RESEARCH | 1991年 / 19卷 / 07期

关键词：

D O I：

10.1093/nar/19.7.1627

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：

Calf thymus DNA polymerase alpha (pol alpha) and bacteriophage T4 DNA polymerase (pol T4) were exploited as model enzymes to investigate the molecular mechanism of inhibitory action of N2-(p-n-butylphenyl)dGTP (BuPdGTP) and 2-(p-n-butylanilino)dATP (BuAdATP) on the BuPdNTP-susceptible alpha polymerase family. Kinetic analysis of inhibition of pol alpha with mixtures of complementary and non-complementary template: primers indicated that both nucleotides induced the formation of a polymerase: inhibitor: primer-template complex. Primer extension experiments using the guanine form as the model analog indicated that pol alpha cannot utilize these nucleotides to extend primer termini. In contrast, pol T4 polymerized BuPdGTP, indicating that resistance to polymerization is not a common feature of the inhibitor mechanism among the broad membership of the alpha polymerase family.

引用

页码：1627 / 1632

页数：6

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