DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange

被引：51

作者：

Ishida, Takako ^{[1
]}

Takizawa, Yoshimasa ^{[1
]}

Kainuma, Takashi ^{[1
]}

Inoue, Jin ^{[2
]}

Mikawa, Tsutomu ^{[2
,3
]}

Shibata, Takehiko ^{[2
]}

Suzuki, Hidekazu ^{[4
]}

Tashiro, Satoshi ^{[4
]}

Kurumizaka, Hitoshi ^{[1
]}

机构：

[1] Waseda Univ, Struct Biol Lab, Grad Sch Adv Sci & Engn, Shinjuku Ku, Tokyo 1628480, Japan

[2] RIKEN, Adv Sci Inst, Wako, Saitama 3510198, Japan

[3] RIKEN, SPring Ctr 8, Sayo, Hyogo 6795148, Japan

[4] Hiroshima Univ, Dept Cellular Biol, Res Inst Radiat Biol & Med, Minami Ku, Hiroshima 7348553, Japan

来源：

NUCLEIC ACIDS RESEARCH | 2009年 / 37卷 / 10期

关键词：

HUMAN RAD51 PROTEIN; SINGLE NUCLEOTIDE POLYMORPHISM; N-TERMINAL DOMAIN; DNA-BINDING; BREAST-CANCER; 5'-UNTRANSLATED REGION; RECOMBINATION; BRCA2; OVEREXPRESSION; MUTATION;

D O I：

10.1093/nar/gkp200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RAD51, an essential eukaryotic DNA recombinase, promotes homologous pairing and strand exchange during homologous recombination and the recombinational repair of double strand breaks. Mutations that up- or down-regulate RAD51 gene expression have been identified in several tumors, suggesting that inappropriate expression of the RAD51 activity may cause tumorigenesis. To identify chemical compounds that affect the RAD51 activity, in the present study, we performed the RAD51-mediated strand exchange assay in the presence of 185 chemical compounds. We found that 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS) efficiently inhibited the RAD51-mediated strand exchange. DIDS also inhibited the RAD51-mediated homologous pairing in the absence of RPA. A surface plasmon resonance analysis revealed that DIDS directly binds to RAD51. A gel mobility shift assay showed that DIDS significantly inhibited the DNA-binding activity of RAD51. Therefore, DIDS may bind near the DNA binding site(s) of RAD51 and compete with DNA for RAD51 binding.

引用

页码：3367 / 3376

页数：10

共 44 条

[1] The N-terminal domain of the human Rad51 protein binds DNA: Structure and a DNA binding surface as revealed by NMR [J].

Aihara, H ;

Ito, Y ;

Kurumizaka, H ;

Yokoyama, S ;

Shibata, T .

JOURNAL OF MOLECULAR BIOLOGY, 1999, 290 (02) :495-504

[2] Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro [J].

Baumann, P ;

Benson, FE ;

West, SC .

CELL, 1996, 87 (04) :757-766

[3]

Blasiak J, 2003, ACTA BIOCHIM POL, V50, P249

[4]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[5] Multiscale analysis of a cantilever with a contact boundary [J].

Chen, Li-Qun .

IUTAM SYMPOSIUM ON MULTISCALE PROBLEMS IN MULTIBODY SYSTEM CONTACTS, 2007, 1 :11-21

[6] The importance of repairing stalled replication forks [J].

Cox, MM ;

Goodman, MF ;

Kreuzer, KN ;

Sherratt, DJ ;

Sandler, SJ ;

Marians, KJ .

NATURE, 2000, 404 (6773) :37-41

[7] Role of BRCA2 in control of the RAD51 recombination and DNA repair protein [J].

Davies, AA ;

Masson, JY ;

Mcllwraith, MJ ;

Stasiak, AZ ;

Stasiak, A ;

Venkitaraman, AR ;

West, SC .

MOLECULAR CELL, 2001, 7 (02) :273-282

[8] Mechanism of eukaryotic homologous recombination [J].

Filippo, Joseph San ;

Sung, Patrick ;

Klein, Hannah .

ANNUAL REVIEW OF BIOCHEMISTRY, 2008, 77 :229-257

[9] BRCA2 BRC motifs bind RAD51-DNA filaments [J].

Galkin, VE ;

Esashi, F ;

Yu, X ;

Yang, SX ;

West, SC ;

Egelman, EH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (24) :8537-8542

[10] Activities of human recombination protein Rad51 [J].

Gupta, RC ;

Bazemore, LR ;

Golub, EI ;

Radding, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (02) :463-468

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