Human SNM1A suppresses the DNA repair defects of yeast pso2 mutants

被引：49

作者：

Hazrati, Ali ^{[2
]}

Ramis-Castelitort, Marc ^{[1
,3
,4
]}

Sarkar, Sovan ^{[1
]}

Barber, Louise J. ^{[2
]}

Schofield, Christopher J. ^{[3
,4
]}

Hartley, John A. ^{[2
]}

McHugh, Peter J. ^{[1
]}

机构：

[1] Univ Oxford, Weatherall Inst Mol Med, Canc Res UK Labs, John Radcliffe Hosp, Oxford OX3 9DS, England

[2] UCL, Sch Med, Dept Oncol, Canc Res UK Drug DNA Interact Res Grp, London W1W 7BS, England

[3] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England

[4] Univ Oxford, Dept Chem, Oxford Ctr Mol Sci, Oxford OX1 3TA, England

来源：

DNA REPAIR | 2008年 / 7卷 / 02期

关键词：

pso2; snm1; metallo-beta-lactamase domain; interstrand cross-links; homologous recombination; nuclease;

D O I：

10.1016/j.dnarep.2007.09.013

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Pso2/Snm1 plays a key role in the repair of DNA interstrand cross-links in yeast. Human cells possess three orthologues of Pso2; SNM1A, SNM1B/Apollo and SNM1C/Artemis. Studies using mammalian cells disrupted or depleted for these genes have yielded equivocal evidence that any of these is a true functional homologues of the yeast gene. Here we show that ectopic expression of only one of the three human orthologues, hSNM1A, effectively suppresses the sensitivity of yeast pso2 (snm1) disruptants to cross-linking agents. Two other phenotypes of the pso2 mutants are also partially rescued by ectopic expression of hSNM1A, namely the double-strand repair break defect observed during cross-link processing in pso2 cells, as well as the spontaneous intrachromatid recombination defect of pso2 msh2 double mutants. Finally, we show that recombinant hSNM1A is a 5'-exonuclease, as also recently reported for the yeast Pso2 protein. Together our data suggest that hSnm1A is a functional homologue of yeast Pso2/Snm1. (c) 2007 Elsevier B.V. All rights reserved.

引用

页码：230 / 238

页数：9

共 35 条

[1] Snm1-deficient mice exhibit accelerated tumorigenesis and susceptibility to infection [J].

Ahkter, S ;

Richie, CT ;

Zhang, NX ;

Behringer, RR ;

Zhu, CM ;

Legerski, RJ .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (22) :10071-10078

[2] Deficiency in SNM1 abolishes an early mitotic checkpoint induced by spindle stress [J].

Akhter, S ;

Richie, CT ;

Deng, JM ;

Brey, E ;

Zhang, XS ;

Patrick, C ;

Behringer, RR ;

Legerski, RJ .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (23) :10448-10455

[3] Conserved domains in DNA repair proteins and evolution of repair systems [J].

Aravind, L ;

Walker, DR ;

Koonin, EV .

NUCLEIC ACIDS RESEARCH, 1999, 27 (05) :1223-1242

[4] A Rad52 homolog is required for RAD51-independent mitotic recombination in Saccharomyces cerevisiae [J].

Bai, Y ;

Symington, LS .

GENES & DEVELOPMENT, 1996, 10 (16) :2025-2037

[5] DNA interstrand cross-link repair in the Saccharomyces cerevisiae cell cycle:: Overlapping roles for PSO2 (SNM1) with MutS factors and EXO1 during S phase [J].

Barber, LJ ;

Ward, TA ;

Hartley, JA ;

McHugh, PJ .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (06) :2297-2309

[6] Initiation of DNA interstrand cross-link repair in humans: the nucleotide excision repair system makes dual incisions 5' to the cross-linked base and removes a 22- to 28-nucleotide-long damage-free strand [J].

Bessho, T ;

Mu, D ;

Sancar, A .

MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (12) :6822-6830

[7] Metallo-β-lactamase fold within nucleic acids processing enzymes:: the β-CASP family [J].

Callebaut, I ;

Moshous, D ;

Mornon, JP ;

de Villartay, JP .

NUCLEIC ACIDS RESEARCH, 2002, 30 (16) :3592-3601

[8] THE 3-D STRUCTURE OF A ZINC METALLO-BETA-LACTAMASE FROM BACILLUS-CEREUS REVEALS A NEW-TYPE OF PROTEIN FOLD [J].

CARFI, A ;

PARES, S ;

DUEE, E ;

GALLENI, M ;

DUEZ, C ;

FRERE, JM ;

DIDEBERG, O .

EMBO JOURNAL, 1995, 14 (20) :4914-4921

[9] Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells [J].

De Silva, IU ;

McHugh, PJ ;

Clingen, PH ;

Hartley, JA .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (21) :7980-7990

[10] Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation [J].

Demuth, I ;

Digweed, M ;

Concannon, P .

ONCOGENE, 2004, 23 (53) :8611-8618

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