Chinese hamster cell mutant, V-C8, a model for analysis of Brca2 function

Mutation Research
Wouter W WiegantMałgorzata Z Zdzienicka

Abstract

The previously described Chinese hamster cell mutant V-C8 that is defective in Brca2 shows a very complex phenotype, including increased sensitivity towards a wide variety of DNA damaging agents, chromosomal instability, abnormal centrosomes and impaired formation of Rad51 foci in response to DNA damage. Here, we demonstrate that V-C8 cells display biallelic nonsense mutations in Brca2, one in exon 15 and the other in exon 16, both resulting in truncated Brca2 proteins. We generated several independent mitomycin C (MMC)-resistant clones from V-C8 cells that had acquired an additional mutation leading to the restoration of the open reading frame of one of the Brca2 alleles. In two of these revertants, V-C8-Rev 1 and V-C8-Rev 6, the reversions lead to the wild-type Brca2 sequence. The V-C8 revertants did not gain the entire wild-type phenotype and still show a 2.5-fold increased sensitivity to mitomycin C (MMC), higher levels of spontaneous and MMC-induced chromosomal aberrations, as well as abnormal centrosomes when compared to wild-type cells. Our results suggest that Brca2 heterozygosity in hamster cells primarily gives rise to sensitivity to DNA cross-linking agents, especially chromosomal instability, a feature that might al...Continue Reading

References

May 15, 1997·Genes & Development·A SuzukiT W Mak
Oct 10, 1997·Nucleic Acids Research·S BuchhopC C Harris
Aug 5, 1999·Journal of the National Cancer Institute·UNKNOWN Breast Cancer Linkage Consortium
Aug 17, 1999·International Journal of Cancer. Journal International Du Cancer·M SantarosaA Viel
Jan 5, 2002·Molecular and Cellular Biology·Maria Kraakman-van der ZwetMalgorzata Z Zdzienicka
Jan 25, 2002·International Journal of Cancer. Journal International Du Cancer·Thomas A BuchholzWilliam A Brock
May 22, 2002·International Journal of Radiation Biology·B NieuwenhuisH H Kampinga
Jun 18, 2002·Science·Niall G HowlettAlan D D'Andrea
Nov 21, 2002·Nature·Luca PellegriniAshok R Venkitaraman
May 28, 2003·DNA Repair·John Thacker, Małgorzata Z Zdzienicka
Aug 21, 2003·Human Molecular Genetics·Madhuri WarrenAlan Ashworth
Nov 14, 2003·Mutagenesis·Maria Kraakman-van der ZwetMałgorzata Z Zdzienicka
May 18, 2004·Trends in Genetics : TIG·Pascale BertrandBernard S Lopez
Dec 3, 2005·EMBO Reports·Carmen Arias-LopezAugusto Silva

❮ Previous
Next ❯

Citations

May 22, 2010·The Journal of Biological Chemistry·Jia LiuMichael M Seidman
Dec 14, 2011·Genome Integrity·Ester SapirPredrag Slijepcevic
Dec 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Therese WilhelmBernard S Lopez
Feb 5, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M TavecchioG Damia
Mar 2, 2012·International Journal of Cancer. Journal International Du Cancer·Rebeka SultanaSrinivasan Madhusudan
Jan 6, 2011·Cancer Science·Kiranjit K DhillonToshiyasu Taniguchi
May 4, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Sha XiaoTahar van der Straaten
Aug 17, 2016·Endocrine-related Cancer·Kiranjit K DhillonChristopher J Lord
Sep 12, 2017·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Yosuke NakagawaEiichiro Mori
Jun 20, 2018·Nucleic Acids Research·Denisse Carvajal-MaldonadoAlessandro Vindigni
Jan 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eike Gallmeier, Scott E Kern
Jun 17, 2010·Cancer Research·Ponnari GottipatiThomas Helleday
Dec 20, 2007·Journal of Cell Science·Fayza DaboussiBernard S Lopez

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.