A model for a umuDC-dependent prokaryotic DNA danage checkpoint

被引:128
作者
Opperman, T [1 ]
Murli, S [1 ]
Smith, BT [1 ]
Walker, GC [1 ]
机构
[1] MIT, Dept Biol, Cambridge, MA 02139 USA
关键词
D O I
10.1073/pnas.96.16.9218
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
The products of the Escherichia coli umuDC operon are required for translesion synthesis, the mechanistic basis of most mutagenesis caused by UV radiation and many chemicals. The UmuD protein shares homology with LexA, the repressor of SOS-regulated loci, and similarly undergoes a facilitated autodigestion on interaction with the RecA/single-stranded DNA nucleoprotein filaments formed after a fell experiences DNA damage. This cleavage, in which Ser-60 of UmuD acts as the nucleophile, produces UmuD', the form active in translesion synthesis. Expression of the noncleavable UmuD(S60A) protein and UmuC was found to increase survival after UV irradiation, despite the inability of the UmuD(S60A) protein to participate in translesion synthesis; this survival increase is uvr(+) dependent. Additional observations that expression of the UmuD(S60A) protein and UmuC delayed the resumption of DNA replication and cell growth after UV irradiation lead us to propose that the uncleaved UmuD protein and UmuC delay the resumption of DNA replication, thereby allowing nucleotide excision repair additional time to repair the damage accurately before replication is attempted. After a UV dose of 20 J/m(2), uncleaved UmuD is the predominant form for approximately 20 min, after which UmuD' becomes the predominant form, suggesting that the umuDC gene products play two distinct and temporally separated roles in DNA damage tolerance, the first in cell-cycle control and the second in translesion synthesis over unrepaired or irreparable lesions. The relationship of these observations to the eukaryotic DNA damage checkpoint is discussed.
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页码:9218 / 9223
页数:6
相关论文
共 56 条
[1]   SUBSTITUTION OF UMUD' FOR UMUD DOES NOT AFFECT SOS MUTAGENESIS [J].
BAILONE, A ;
SOMMER, S ;
KNEZEVIC, J ;
DEVORET, R .
BIOCHIMIE, 1991, 73 (04) :471-478
[2]   DOMINANT NEGATIVE UMUD MUTATIONS DECREASING RECA-MEDIATED CLEAVAGE SUGGEST ROLES FOR INTACT UMUD IN MODULATION OF SOS MUTAGENESIS [J].
BATTISTA, JR ;
OHTA, T ;
NOHMI, T ;
SUN, W ;
WALKER, GC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (18) :7190-7194
[3]   ARE THERE DNA-DAMAGE CHECKPOINTS IN ESCHERICHIA-COLI [J].
BRIDGES, BA .
BIOESSAYS, 1995, 17 (01) :63-70
[4]  
BRIDGES BA, 1975, MUTAT RES, V29, P497
[5]   UMUD MUTAGENESIS PROTEIN OF ESCHERICHIA-COLI - OVERPRODUCTION, PURIFICATION, AND CLEAVAGE BY RECA [J].
BURCKHARDT, SE ;
WOODGATE, R ;
SCHEUERMANN, RH ;
ECHOLS, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (06) :1811-1815
[6]   COEXPRESSION OF UMUD' WITH UMUC SUPPRESSES THE UV MUTAGENESIS DEFICIENCY OF GROE MUTANTS [J].
DONNELLY, CE ;
WALKER, GC .
JOURNAL OF BACTERIOLOGY, 1992, 174 (10) :3133-3139
[7]   THE GROE GENE-PRODUCTS OF ESCHERICHIA-COLI ARE DISPENSABLE FOR MUCA(+)B(+)-DEPENDENT UV MUTAGENESIS [J].
DONNELLY, CE ;
MURLI, S ;
WALKER, GC .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1994, 309 (02) :225-233
[8]  
ECHOLS H, 1991, ANNU REV BIOCHEM, V60, P477, DOI 10.1146/annurev.biochem.60.1.477
[9]   SOS FUNCTIONS, CANCER AND INDUCIBLE EVOLUTION [J].
ECHOLS, H .
CELL, 1981, 25 (01) :1-2
[10]   Cell cycle checkpoints: Preventing an identity crisis [J].
Elledge, SJ .
SCIENCE, 1996, 274 (5293) :1664-1672