SLOW REPAIR OF PYRIMIDINE DIMERS AT P53 MUTATION HOTSPOTS IN SKIN-CANCER

被引:259
作者
TORNALETTI, S [1 ]
PFEIFER, GP [1 ]
机构
[1] BECKMAN RES INST CITY HOPE,DUARTE,CA 91010
关键词
D O I
10.1126/science.8128225
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
Ultraviolet light has been linked with the development of human skin cancers. Such cancers often exhibit mutations in the p53 tumor suppressor gene. Ligation-mediated polymerase chain reaction was used to analyze at nucleotide resolution the repair of cyclobutane pyrimidine dimers along the p53 gene in ultraviolet-irradiated human fibroblasts. Repair rates at individual nucleotides were highly variable and sequence-dependent. Slow repair was seen at seven of eight positions frequently mutated in skin cancer, suggesting that repair efficiency may strongly contribute to the mutation spectrum in a cancer-associated gene.
引用
收藏
页码:1436 / 1438
页数:3
相关论文
共 30 条
[1]   SITE AND STRAND SPECIFICITY OF UVB MUTAGENESIS IN THE SUP4-O GENE OF YEAST [J].
ARMSTRONG, JD ;
KUNZ, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (22) :9005-9009
[2]   DNA-REPAIR IN AN ACTIVE GENE - REMOVAL OF PYRIMIDINE DIMERS FROM THE DHFR GENE OF CHO CELLS IS MUCH MORE EFFICIENT THAN IN THE GENOME OVERALL [J].
BOHR, VA ;
SMITH, CA ;
OKUMOTO, DS ;
HANAWALT, PC .
CELL, 1985, 40 (02) :359-369
[3]  
BRASH DE, 1988, PHOTOCHEM PHOTOBIOL, V48, P59
[4]  
BRASH E, 1991, P NATL ACAD SCI USA, V88, P1014
[5]   RESTRICTED ULTRAVIOLET MUTATIONAL SPECTRUM IN A SHUTTLE VECTOR PROPAGATED IN XERODERMA PIGMENTOSUM-CELLS [J].
BREDBERG, A ;
KRAEMER, KH ;
SEIDMAN, MM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (21) :8273-8277
[6]  
DEFROMENTEL CC, 1992, GENE CHROMOSOME CANC, V4, P1
[7]   THE SPECIFICITY OF UV-INDUCED MUTATIONS AT AN ENDOGENOUS LOCUS IN MAMMALIAN-CELLS [J].
DROBETSKY, EA ;
GROSOVSKY, AJ ;
GLICKMAN, BW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) :9103-9107
[8]  
EVANS MK, 1993, CANCER RES, V53, P5377
[9]   DNA-REPAIR RATES MAPPED ALONG THE HUMAN PGK1 GENE AT NUCLEOTIDE RESOLUTION [J].
GAO, SW ;
DROUIN, R ;
HOLMQUIST, GP .
SCIENCE, 1994, 263 (5152) :1438-1440
[10]   COMPARISON OF ULTRAVIOLET IRRADIATION-INDUCED MUTAGENESIS OF THE LACI GENE IN ESCHERICHIA-COLI AND IN HUMAN-293 CELLS [J].
HSIA, HC ;
LEBKOWSKI, JS ;
LEONG, PM ;
CALOS, MP ;
MILLER, JH .
JOURNAL OF MOLECULAR BIOLOGY, 1989, 205 (01) :103-113