High levels of wild-type BRCA2 suppress homologous recombination

Journal of Molecular Biology
Alissa C MagwoodMark D Baker

Abstract

Endogenous levels of the BRCA2 (breast cancer susceptibility 2) protein promote homologous recombination by regulating the essential strand exchange protein RAD51. To examine BRCA2 function in homologous recombination, we expressed human BRCA2 in control mouse hybridoma cells, as well as those that were depleted of endogenous Brca2 by small interfering RNA. With moderate human BRCA2 expression, homologous recombination was stimulated. Conversely, a higher level of BRCA2 reduced homologous recombination and DNA-damage-induced Rad51 foci formation. Cells expressing high levels of BRCA2 feature normal growth, increased sensitivity to mitomycin C, and increased illegitimate recombination. BRCA2-overexpressing cells are also characterized by suppression of p53 transcriptional regulation and a corresponding reduction in the expression of the p53-responsive genes Noxa and p21. Notably, in cells expressing high levels of BRCA2, small interfering RNA depletion of human BRCA2 or ectopic expression of Rad51 increases homologous recombination and decreases illegitimate recombination. Thus, high levels of wild-type BRCA2 perturb Rad51-mediated homologous recombination, and relatively normal recombination responses can be restored by rebalan...Continue Reading

References

Sep 1, 1990·Molecular and Cellular Biology·M J ShulmanC Collins
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M D BakerM J Shulman
Jul 2, 1973·European Journal of Biochemistry·M Gross-BellardP Chambon
Mar 1, 1996·Nature Genetics·J T HoltR A Jensen
Jun 1, 1996·Nature Genetics·J M LancasterP A Futreal
Jun 1, 1996·Nature Genetics·Y MikiY Nakamura
Nov 8, 1996·The Journal of Biological Chemistry·P Sung, S A Stratton
Jan 1, 1997·Human Molecular Genetics·G BignellR Wooster
Oct 10, 1997·Nucleic Acids Research·S BuchhopC C Harris
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·P L ChenW H Lee
Jul 29, 1998·International Journal of Cancer. Journal International Du Cancer·S FanE M Rosen
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·L Y MarmorsteinS A Aaronson
Aug 24, 1999·Gene Therapy·R J Yáñez, A C Porter
Sep 28, 1999·Oncogene·I BiècheR Lidereau
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·B H SpainI M Verma
Mar 10, 2001·Molecular Cell·M E MoynahanM Jasin
May 10, 2001·Current Opinion in Cell Biology·A R Venkitaraman
Feb 8, 2002·Cell·Ashok R Venkitaraman
Jul 26, 2002·Oncogene·Florence LarminatMartine Defais
Nov 21, 2002·Nature·Luca PellegriniAshok R Venkitaraman
Feb 28, 2003·Oncogene·Madalena TarsounasStephen C West
Jun 6, 2003·The New England Journal of Medicine·Richard Wooster, Barbara L Weber
Aug 6, 2003·American Journal of Human Genetics·Deborah ThompsonDavid E Goldgar
Aug 13, 2003·The Journal of Biological Chemistry·Patrick SungMichael G Sehorn
Sep 10, 2003·Gene Therapy·H WürteleP Chartrand
Dec 9, 2003·Development·Shyam K SharanMary Ann Handel
Jun 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Vitold E GalkinEdward H Egelman
Mar 4, 2006·The Journal of Biological Chemistry·Joseph San FilippoPatrick Sung
Aug 18, 2006·Nucleic Acids Research·Mahmud K K ShivjiAshok R Venkitaraman

❮ Previous
Next ❯

Citations

Nov 15, 2015·Cell Cycle·Juan S MartinezAura Carreira
Aug 20, 2014·BioMed Research International·Giulia GirolimettiDaniela Turchetti
Mar 16, 2019·Scientific Reports·Charles X WangAlexander V Mazin
Dec 19, 2016·Chemical Research in Toxicology·Xiufang SongYang Song

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

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.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.