Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair

被引:745
作者
Hofmann, RM [1 ]
Pickart, CM [1 ]
机构
[1] Johns Hopkins Univ, Sch Publ Hlth, Dept Biochem, Baltimore, MD 21205 USA
关键词
D O I
10.1016/S0092-8674(00)80575-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Ubiquitin-conjugating enzyme variant (UEV) proteins resemble ubiquitin-conjugating enzymes (E2s) but lack the defining E2 active-site residue. The MMS2-encoded UEV protein has been genetically implicated in error-free postreplicative DNA repair in Saccharomyces cerevisiae. We show that Mms2p forms a specific heteromeric complex with the UBC13-encoded E2 and is required for the Ubc13p-dependent assembly of polyubiquitin chains linked through lysine 63. A ubc13 yeast strain is UV sensitive, and single, double, and triple mutants of the UBC13, MMS2, and ubiquitin (ubiK63R) genes display a comparable phenotype. These findings support a model in which an Mms2p/Ubc13p complex assembles novel polyubiquitin chains for signaling in DNA repair, and they suggest that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation.
引用
收藏
页码:645 / 653
页数:9
相关论文
共 54 条
[1]
A METHOD FOR GENE DISRUPTION THAT ALLOWS REPEATED USE OF URA3 SELECTION IN THE CONSTRUCTION OF MULTIPLY DISRUPTED YEAST STRAINS [J].
ALANI, E ;
CAO, L ;
KLECKNER, N .
GENETICS, 1987, 116 (04) :541-545
[2]
Ausubel F.A., 1997, CURRENT PROTOCOLS MO, DOI DOI 10.1.4
[3]
SPECIFIC COMPLEX-FORMATION BETWEEN YEAST RAD6 AND RAD18 PROTEINS - A POTENTIAL MECHANISM FOR TARGETING RAD6 UBIQUITIN-CONJUGATING ACTIVITY TO DNA-DAMAGE SITES [J].
BAILLY, V ;
LAMB, J ;
SUNG, P ;
PRAKASH, S ;
PRAKASH, L .
GENES & DEVELOPMENT, 1994, 8 (07) :811-820
[4]
Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities [J].
Bailly, V ;
Lauder, S ;
Prakash, S ;
Prakash, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (37) :23360-23365
[5]
Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting [J].
Beal, R ;
Deveraux, Q ;
Xia, G ;
Rechsteiner, M ;
Pickart, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) :861-866
[6]
The hydrophobic effect contributes to polyubiquitin chain recognition [J].
Beal, RE ;
Toscano-Cantaffa, D ;
Young, P ;
Rechsteiner, M ;
Pickart, CM .
BIOCHEMISTRY, 1998, 37 (09) :2925-2934
[7]
MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway [J].
Broomfield, S ;
Chow, BL ;
Xiao, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5678-5683
[8]
A MULTIUBIQUITIN CHAIN IS CONFINED TO SPECIFIC LYSINE IN A TARGETED SHORT-LIVED PROTEIN [J].
CHAU, V ;
TOBIAS, JW ;
BACHMAIR, A ;
MARRIOTT, D ;
ECKER, DJ ;
GONDA, DK ;
VARSHAVSKY, A .
SCIENCE, 1989, 243 (4898) :1576-1583
[9]
MULTIPLE UBIQUITIN-CONJUGATING ENZYMES PARTICIPATE IN THE IN-VIVO DEGRADATION OF THE YEAST MAT-ALPHA-2 REPRESSOR [J].
CHEN, P ;
JOHNSON, P ;
SOMMER, T ;
JENTSCH, S ;
HOCHSTRASSER, M .
CELL, 1993, 74 (02) :357-369
[10]
CHEN ZJ, 1990, J BIOL CHEM, V265, P21835