BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution

Nucleic Acids Research
Chu-Xia Deng

Abstract

Germline mutations of the breast cancer associated gene 1 (BRCA1) predispose women to breast and ovarian cancers. BRCA1 is a large protein with multiple functional domains and interacts with numerous proteins that are involved in many important biological processes/pathways. Mounting evidence indicates that BRCA1 is involved in all phases of the cell cycle and regulates orderly events during cell cycle progression. BRCA1 deficiency, consequently causes abnormalities in the S-phase checkpoint, the G(2)/M checkpoint, the spindle checkpoint and centrosome duplication. The genetic instability caused by BRCA1 deficiency, however, also triggers cellular responses to DNA damage that blocks cell proliferation and induces apoptosis. Thus BRCA1 mutant cells cannot develop further into full-grown tumors unless this cellular defense is broken. Functional analysis of BRCA1 in cell cycle checkpoints, genome integrity, DNA damage response (DDR) and tumor evolution should benefit our understanding of the mechanisms underlying BRCA1 associated tumorigenesis, as well as the development of therapeutic approaches for this lethal disease.

References

Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·T MikiS A Aaronson
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Mar 1, 1996·Nature Genetics·J T HoltR A Jensen
Jan 31, 1997·Science·R B Nicklas
Apr 24, 1997·Nature·K W Kinzler, B Vogelstein
May 15, 1997·The New England Journal of Medicine·J P StruewingM A Tucker
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·H Ruffner, I M Verma
Mar 11, 1999·Current Opinion in Genetics & Development·A Amon
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·R I Yarden, L C Brody
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·O N AprelikovaE T Liu
Nov 5, 1999·The Nursing Spectrum·K A Calzone
Nov 5, 1999·Current Opinion in Oncology·A J AlbergK J Helzlsouer
Dec 2, 1999·Molecular and Cellular Endocrinology·M Schuyer, E M Berns
Jan 15, 2000·Molecular Cell·R ScullyD M Livingston
Aug 5, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·C X Deng, S G Brodie
Apr 21, 2001·Molecular and Cellular Biology·B XuM B Kastan
Oct 5, 2001·Trends in Genetics : TIG·S G Brodie, C X Deng

❮ Previous
Next ❯

Citations

May 7, 2009·Breast Cancer Research and Treatment·Tyler LahusenAnna T Riegel
Dec 15, 2011·Breast Cancer Research and Treatment·Miljana TanicBeatriz Martínez-Delgado
Apr 21, 2010·Cancer Metastasis Reviews·Andrea TinelliVito Lorusso
Oct 25, 2012·Cancer Metastasis Reviews·Jennifer Dine, Chu-Xia Deng
Jul 20, 2007·Current Treatment Options in Oncology·Diana S RosmanBoris Pasche
Nov 16, 2011·Neurotoxicity Research·Jeriel T R KeeneyD Allan Butterfield
Jul 17, 2013·Best Practice & Research. Clinical Endocrinology & Metabolism·Navneet SinghSubhas Chakrabarty
Apr 30, 2013·Cancer Letters·Geun-Hyoung HaEun-Kyoung Yim Breuer
May 21, 2013·DNA Repair·Yannick Auclair, Stéphane Richard
Sep 8, 2010·Cell Research·Vivek ShuklaChu-Xia Deng
Sep 29, 2011·Nature Medicine·Suhwan ChangShyam K Sharan
Nov 17, 2006·Nature Reviews. Cancer·Lauren M F MerloCarlo C Maley
Mar 23, 2011·Nature Reviews. Clinical Oncology·Ralph R Weichselbaum, Samuel Hellman
May 11, 2010·Nature Structural & Molecular Biology·Peter BouwmanJos Jonkers
Nov 26, 2010·Nature Structural & Molecular Biology·Li-Jun DiKevin Gardner
Dec 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Latarsha J ReidThomas Ludwig
Mar 9, 2010·The Journal of Biological Chemistry·Janet C Koon, Terrance J Kubiseski
May 16, 2008·The Journal of Biological Chemistry·David FoxRachel E Klevit
Nov 1, 2008·Carcinogenesis·Shian-Ling DingChen-Yang Shen
Dec 26, 2006·Nucleic Acids Research·Michael HölzelDirk Eick
Sep 8, 2010·Nucleic Acids Research·Astrid S Block-SchmidtHolger Puchta
Mar 11, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Nancie PetrucelliGerald L Feldman
Jun 21, 2007·Journal of the Royal Society, Interface·Natalia L KomarovaFrederic Y M Wan
May 23, 2007·Molekuliarnaia biologiia·B P Kopnin
Jun 25, 2008·Annual Review of Biophysics·Vladimir N UverskyA Keith Dunker
Sep 25, 2007·Annual Review of Genomics and Human Genetics·Peter J McKinnon, Keith W Caldecott
Jan 14, 2010·Cancer Research·Adriana De SierviKevin Gardner
Sep 10, 2011·Therapeutic Advances in Medical Oncology·Georgios IoannidisJohn Souglakos

❮ Previous
Next ❯

Methods Mentioned

BETA
antisense oligonucleotides
transfection
transgenic
targeted mutations

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.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.