Home LiteratureArticle Details
PMID: 9560268 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 9 ·1998-04-28 ·Pages 5287-92

Chen PL, Chen CF, Chen Y, Xiao J, Sharp ZD, Lee WH

Abstract

The BRCA2 gene was identified based on its involvement in familial breast cancer. The analysis of its sequence predicts that the gene encodes a protein with 3,418 amino acids but provides very few clues pointing to its biological function. In an attempt to address this question, specific antibodies were prepared that identified the gene product of BRCA2 as a 390-kDa nuclear protein. Furthermore, direct binding of human RAD51 to each of the four single 30-amino acid BRC repeats located at the 5' portion of exon 11 of BRCA2 was demonstrated. Such an interaction is significant, as BRCA2 and RAD51 can be reciprocally coimmunoprecipitated by each of the individual, specific antibodies and form complexes in vivo. Inferring from the function of RAD51 in DNA repair, human pancreatic cancer cells, Capan-1, expressing truncated BRCA2 were shown to be hypersensitive to methyl methanesulfonate (MMS) treatment. Exogenous expression of wild-type BRCA2, but not BRC-deleted mutants, in Capan-1 cells confers resistance to MMS treatment. These results suggest that the interaction between the BRC repeats of BRCA2 and RAD51 is critical for cellular response to DNA damage caused by MMS.

MeSH Terms
BRCA2 Protein Breast Neoplasms DNA Damage DNA Repair DNA, Complementary/genetics DNA, Neoplasm/genetics DNA-Binding Proteins/metabolism Female Humans Immunologic Techniques Methyl Methanesulfonate Molecular Weight Neoplasm Proteins/chemistry,physiology Nuclear Proteins/physiology Protein Binding Rad51 Recombinase Repetitive Sequences, Nucleic Acid Transcription Factors/chemistry,physiology Tumor Cells, Cultured
Chemicals
BRCA2 Protein DNA, Complementary DNA, Neoplasm DNA-Binding Proteins Neoplasm Proteins Nuclear Proteins Transcription Factors Methyl Methanesulfonate RAD51 protein, human Rad51 Recombinase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chen P L
Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center, San Antonio, TX 78245, USA.
Chen C F
Chen Y
Xiao J
Sharp Z D
Lee W H
References (36)
36 references, click to expand
  1. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein.
    Cell. 1992 May 1;69(3):457-70 PMID: 1581961
  2. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins.
    FASEB J. 1997 Jan;11(1):68-76 PMID: 9034168
  3. A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes.
    Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6577-80 PMID: 8341671
  4. Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA.
    Nat Genet. 1993 Jul;4(3):239-43 PMID: 8358431
  5. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
    Cell. 1993 Dec 3;75(5):1027-38 PMID: 8252616
  6. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer.
    Cell. 1993 Dec 17;75(6):1215-25 PMID: 8261515
  7. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13.
    Science. 1994 Sep 30;265(5181):2088-90 PMID: 8091231
  8. BRCA1 mutations in primary breast and ovarian carcinomas.
    Science. 1994 Oct 7;266(5182):120-2 PMID: 7939630
  9. Homotypic and heterotypic protein associations control Rad51 function in double-strand break repair.
    Genes Dev. 1994 Nov 1;8(21):2552-62 PMID: 7958917
  10. The amino-terminal region of the retinoblastoma gene product binds a novel nuclear matrix protein that co-localizes to centers for RNA processing.
    J Cell Biol. 1994 Nov;127(3):609-22 PMID: 7525595
  11. Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA.
    EMBO J. 1994 Dec 1;13(23):5764-71 PMID: 7988572
  12. Nuclear foci of mammalian Rad51 recombination protein in somatic cells after DNA damage and its localization in synaptonemal complexes.
    Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2298-302 PMID: 7892263
  13. Complex formation in yeast double-strand break repair: participation of Rad51, Rad52, Rad55, and Rad57 proteins.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6925-9 PMID: 7624345
  14. Identification of the breast cancer susceptibility gene BRCA2.
    Nature. 1995 Dec 21-28;378(6559):789-92 PMID: 8524414
  15. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.
    Nat Genet. 1996 Mar;12(3):333-7 PMID: 8589730
  16. Frequent occurrence of BRCA2 linkage in Icelandic breast cancer families and segregation of a common BRCA2 haplotype.
    Am J Hum Genet. 1996 Apr;58(4):749-56 PMID: 8644738
  17. Mutation analysis in the BRCA2 gene in primary breast cancers.
    Nat Genet. 1996 Jun;13(2):245-7 PMID: 8640237
  18. Internal repeats in the BRCA2 protein sequence.
    Nat Genet. 1996 May;13(1):22-3 PMID: 8673099
  19. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes.
    Nat Genet. 1996 May;13(1):117-9 PMID: 8673089
  20. BRCA1 protein products ... Functional motifs...
    Nat Genet. 1996 Jul;13(3):266-8 PMID: 8673121
  21. Mutations in the BRCA2 gene in hepatocellular carcinomas.
    Cancer Res. 1996 Oct 15;56(20):4575-7 PMID: 8840963
  22. Cell cycle control of BRCA2.
    Cancer Res. 1996 Oct 15;56(20):4590-4 PMID: 8840967
  23. Reduced X-ray resistance and homologous recombination frequencies in a RAD54-/- mutant of the chicken DT40 cell line.
    Cell. 1997 Apr 18;89(2):185-93 PMID: 9108474
  24. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2.
    Nature. 1997 Apr 24;386(6627):804-10 PMID: 9126738
  25. Developmental expression of Brca2 colocalizes with Brca1 and is associated with proliferation and differentiation in multiple tissues.
    Dev Biol. 1997 Apr 15;184(2):385-401 PMID: 9133444
  26. Reconstitution of a MEC1-independent checkpoint in yeast by expression of a novel human fork head cDNA.
    Mol Cell Biol. 1997 Jun;17(6):3037-46 PMID: 9154802
  27. Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos.
    Genes Dev. 1997 May 15;11(10):1226-41 PMID: 9171368
  28. Brca2 is required for embryonic cellular proliferation in the mouse.
    Genes Dev. 1997 May 15;11(10):1242-52 PMID: 9171369
  29. RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51 protein.
    Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6927-32 PMID: 9192668
  30. HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins.
    J Biol Chem. 1997 Sep 19;272(38):24081-7 PMID: 9295362
  31. HEC, a novel nuclear protein rich in leucine heptad repeats specifically involved in mitosis.
    Mol Cell Biol. 1997 Oct;17(10):6049-56 PMID: 9315664
  32. Identification of a RING protein that can interact in vivo with the BRCA1 gene product.
    Nat Genet. 1996 Dec;14(4):430-40 PMID: 8944023
  33. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas.
    Cancer Res. 1996 Dec 1;56(23):5360-4 PMID: 8968085
  34. The BRC repeats are conserved in mammalian BRCA2 proteins.
    Hum Mol Genet. 1997 Jan;6(1):53-8 PMID: 9002670
  35. Association of BRCA1 with Rad51 in mitotic and meiotic cells.
    Cell. 1997 Jan 24;88(2):265-75 PMID: 9008167
  36. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.
    Genes Dev. 1993 Apr;7(4):555-69 PMID: 8384581
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.9.5287
Published
1998-04-28
Pages
5287-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20253
Subset
IM
Grants
NCI NIH HHS · P50 CA058183 · United States
NCI NIH HHS · P50-CA58183 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.9.5287 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2