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Literature DB >> 10837032

Gross chromosomal rearrangements and genetic exchange between nonhomologous chromosomes following BRCA2 inactivation.

V P Yu¹, M Koehler, C Steinlein, M Schmid, L A Hanakahi, A J van Gool, S C West, A R Venkitaraman.

Abstract

Cancer-causing mutations often arise from gross chromosomal rearrangements (GCRs) such as translocations, which involve genetic exchange between nonhomologous chromosomes. Here we show that murine Brca2 has an essential function in suppressing GCR formation after chromosome breakage. Cells that harbor truncated Brca2 spontaneously incur GCRs and genomic DNA breaks during division. They exhibit hypersensitivity to DNA damage by interstrand cross-linkers, which even at low doses trigger aberrant genetic exchange between nonhomologous chromosomes. Therefore, genetic instability in Brca2-deficient cells results from the mutagenic processing of spontaneous or induced DNA damage into gross chromosomal rearrangements, providing a mechanistic basis for cancer predisposition.

Entities: Disease Gene Species

Mesh：

Substances：

Year: 2000 PMID： 10837032 PMCID： PMC316655

Source DB: PubMed Journal: Genes Dev ISSN： 0890-9369 Impact factor: 11.361

38 in total

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

Authors: P L Chen; C F Chen; Y Chen; J Xiao; Z D Sharp; W H Lee
Journal: Proc Natl Acad Sci U S A Date: 1998-04-28 Impact factor: 11.205

2. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas.

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Journal: Cancer Res Date: 1996-12-01 Impact factor: 12.701

3. Expression of BRC repeats in breast cancer cells disrupts the BRCA2-Rad51 complex and leads to radiation hypersensitivity and loss of G(2)/M checkpoint control.

Authors: C F Chen; P L Chen; Q Zhong; Z D Sharp; W H Lee
Journal: J Biol Chem Date: 1999-11-12 Impact factor: 5.157

4. Interstrand cross-links induce DNA synthesis in damaged and undamaged plasmids in mammalian cell extracts.

Authors: L Li; C A Peterson; X Lu; P Wei; R J Legerski
Journal: Mol Cell Biol Date: 1999-08 Impact factor: 4.272

5. BRCA2 and p53 mutations in primary breast cancer in relation to genetic instability.

Authors: S Gretarsdottir; S Thorlacius; R Valgardsdottir; S Gudlaugsdottir; S Sigurdsson; M Steinarsdottir; J G Jonasson; K Anamthawat-Jonsson; J E Eyfjörd
Journal: Cancer Res Date: 1998-03-01 Impact factor: 12.701

6. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2.

Authors: S K Sharan; M Morimatsu; U Albrecht; D S Lim; E Regel; C Dinh; A Sands; G Eichele; P Hasty; A Bradley
Journal: Nature Date: 1997-04-24 Impact factor: 49.962

7. DNA end-joining catalyzed by human cell-free extracts.

Authors: P Baumann; S C West
Journal: Proc Natl Acad Sci U S A Date: 1998-11-24 Impact factor: 11.205

8. Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12-q13.

Authors: J Gudmundsson; G Johannesdottir; J T Bergthorsson; A Arason; S Ingvarsson; V Egilsson; R B Barkardottir
Journal: Cancer Res Date: 1995-11-01 Impact factor: 12.701

9. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.

Authors: J Chen; D P Silver; D Walpita; S B Cantor; A F Gazdar; G Tomlinson; F J Couch; B L Weber; T Ashley; D M Livingston; R Scully
Journal: Mol Cell Date: 1998-09 Impact factor: 17.970

10. Illegitimate recombination induced by DNA double-strand breaks in a mammalian chromosome.

Authors: J W Phillips; W F Morgan
Journal: Mol Cell Biol Date: 1994-09 Impact factor: 4.272

93 in total

Review 1. Homologous DNA recombination in vertebrate cells.

Authors: E Sonoda; M Takata; Y M Yamashita; C Morrison; S Takeda
Journal: Proc Natl Acad Sci U S A Date: 2001-07-17 Impact factor: 11.205

2. Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.

Authors: F Xia; D G Taghian; J S DeFrank; Z C Zeng; H Willers; G Iliakis; S N Powell
Journal: Proc Natl Acad Sci U S A Date: 2001-07-10 Impact factor: 11.205

3. Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions.

Authors: Maria Kraakman-van der Zwet; Wilhelmina J I Overkamp; Rebecca E E van Lange; Jeroen Essers; Annemarie van Duijn-Goedhart; Ingrid Wiggers; Srividya Swaminathan; Paul P W van Buul; Abdellatif Errami; Raoul T L Tan; Nicolaas G J Jaspers; Shyam K Sharan; Roland Kanaar; Malgorzata Z Zdzienicka
Journal: Mol Cell Biol Date: 2002-01 Impact factor: 4.272

4. Repair kinetics of genomic interstrand DNA cross-links: evidence for DNA double-strand break-dependent activation of the Fanconi anemia/BRCA pathway.

Authors: Andreas Rothfuss; Markus Grompe
Journal: Mol Cell Biol Date: 2004-01 Impact factor: 4.272