IXR1, A YEAST PROTEIN THAT BINDS TO PLATINATED DNA AND CONFERS SENSITIVITY TO CISPLATIN

被引:182
作者
BROWN, SJ [1 ]
KELLETT, PJ [1 ]
LIPPARD, SJ [1 ]
机构
[1] MIT, DEPT CHEM, CAMBRIDGE, MA 02139 USA
关键词
D O I
10.1126/science.8342024
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
Structure-specific recognition proteins (SSRPs) bind to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. A yeast gene encoding an SSRP, designated IXR1, was cloned and sequenced. The Ixr1 protein, a member of the high mobility group-box protein family, bound specifically to DNA modified with cisplatin but not inactive platinum compounds. A yeast strain with an inactivated IXR1 gene was half as sensitive to cisplatin and accumulated one-third as many platinum-DNA lesions after treatment with cisplatin as the parental strain. These findings suggest that SSRPs play a role in mediating the cytotoxicity of cisplatin.
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收藏
页码:603 / 605
页数:3
相关论文
共 22 条
[1]  
BROWN SDM, UNPUB
[2]   ISOLATION AND CHARACTERIZATION OF HUMAN CDNA CLONES ENCODING A HIGH MOBILITY GROUP BOX PROTEIN THAT RECOGNIZES STRUCTURAL DISTORTIONS TO DNA CAUSED BY BINDING OF THE ANTICANCER AGENT CISPLATIN [J].
BRUHN, SL ;
PIL, PM ;
ESSIGMANN, JM ;
HOUSMAN, DE ;
LIPPARD, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (06) :2307-2311
[3]  
BRUHN SL, 1990, PROG INORG CHEM, V38, P477
[4]   SYNERGISTIC ACTIVATION BY THE GLUTAMINE-RICH DOMAINS OF HUMAN TRANSCRIPTION FACTOR SP1 [J].
COUREY, AJ ;
HOLTZMAN, DA ;
JACKSON, SP ;
TJIAN, R .
CELL, 1989, 59 (05) :827-836
[5]   A COMPREHENSIVE SET OF SEQUENCE-ANALYSIS PROGRAMS FOR THE VAX [J].
DEVEREUX, J ;
HAEBERLI, P ;
SMITHIES, O .
NUCLEIC ACIDS RESEARCH, 1984, 12 (01) :387-395
[6]  
DIFFLEY JFX, 1992, J BIOL CHEM, V267, P3368
[7]   A CLOSE RELATIVE OF THE NUCLEAR, CHROMOSOMAL HIGH-MOBILITY GROUP PROTEIN HMG1 IN YEAST MITOCHONDRIA [J].
DIFFLEY, JFX ;
STILLMAN, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) :7864-7868
[8]   CHARACTERIZATION OF A DNA DAMAGE-RECOGNITION PROTEIN FROM MAMMALIAN-CELLS THAT BINDS SPECIFICALLY TO INTRASTRAND D(GPG) AND D(APG) DNA ADDUCTS OF THE ANTICANCER DRUG CISPLATIN [J].
DONAHUE, BA ;
AUGOT, M ;
BELLON, SF ;
TREIBER, DK ;
TONEY, JH ;
LIPPARD, SJ ;
ESSIGMANN, JM .
BIOCHEMISTRY, 1990, 29 (24) :5872-5880
[9]   DNA-BINDING PROPERTIES OF THE HMG DOMAIN OF THE LYMPHOID-SPECIFIC TRANSCRIPTIONAL REGULATOR LEF-1 [J].
GIESE, K ;
AMSTERDAM, A ;
GROSSCHEDL, R .
GENES & DEVELOPMENT, 1991, 5 (12B) :2567-2578
[10]  
HUGHES EN, 1992, J BIOL CHEM, V267, P13520