Phenotypic change caused by transcriptional bypass of uracil in nondividing cells

被引:92
作者
Viswanathan, A
You, HJ
Doetsch, PW [1 ]
机构
[1] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Grad Program Genet & Mol Biol, Atlanta, GA 30322 USA
关键词
D O I
10.1126/science.284.5411.159
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cytosine deamination to uracil occurs frequently in cellular DNA. In vitro, RNA polymerase efficiently inserts adenine opposite to uracil, resulting in Ci to A base substitutions. In vivo, uracil could potentially alter transcriptional fidelity, resulting in production of mutant proteins. This study demonstrates that in nondividing Escherichia coli cells, a DNA template base replaced with uracil in a stop codon in the firefly Luciferase gene results in conversion of inactive to active Luciferase, The Level of transcriptional base substitution is dependent on the capacity to repair uracil, These results provide evidence for a DNA damage-dependent, transcription-driven pathway for generating mutant proteins in nondividing cells.
引用
收藏
页码:159 / 162
页数:4
相关论文
共 38 条
[1]   Novenamines as inhibitors of two independent enzymes during DNA replication in a toluenized Escherichia coli cell system [J].
Althaus, IW ;
Kezdy, FJ ;
Peterson, T ;
Spilman, CH ;
Reusser, F .
BIOCHEMICAL PHARMACOLOGY, 1996, 51 (10) :1373-1378
[2]   MUTY DIRECTS MUTATION [J].
BRIDGES, BA .
NATURE, 1995, 375 (6534) :741-741
[3]  
Bridges BA, 1996, CANCER SURV, V28, P155
[4]   THE ORIGIN OF MUTANTS [J].
CAIRNS, J ;
OVERBAUGH, J ;
MILLER, S .
NATURE, 1988, 335 (6186) :142-145
[5]  
CHEN YH, 1993, J BIOL CHEM, V268, P5849
[6]   RETRACTED: Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G (Retracted Article. See vol 308, pg 1740, 2005) [J].
Cooper, PK ;
Nouspikel, T ;
Clarkson, SG ;
Leadon, SA .
SCIENCE, 1997, 275 (5302) :990-993
[7]   PROPHAGE INDUCTION BY DNA TOPOISOMERASE-II POISONS AND REACTIVE-OXYGEN SPECIES - ROLE OF DNA BREAKS [J].
DEMARINI, DM ;
LAWRENCE, BK .
MUTATION RESEARCH, 1992, 267 (01) :1-17
[8]   RECONSTITUTION OF THE DNA-BASE EXCISION-REPAIR PATHWAY [J].
DIANOV, G ;
LINDAHL, T .
CURRENT BIOLOGY, 1994, 4 (12) :1069-1076
[9]  
DOETSCH P, 1998, DNA DAMAGE REPAIR OX, P97
[10]   MUTAGENIC DEAMINATION OF CYTOSINE RESIDUES IN DNA [J].
DUNCAN, BK ;
MILLER, JH .
NATURE, 1980, 287 (5782) :560-561