Mitotic defects in XRCC3 variants T241M and D213N and their relation to cancer susceptibility

Human Molecular Genetics
Anna Renglin LindhThomas Helleday

Abstract

The XRCC3 variant T241M, but not D213N, has been reported to be associated with an increased risk of some cancers. XRCC3 is one out of five RAD51 paralogues and is involved in homologous recombination, as are the BRCA1 and BRCA2 proteins. However, in contrast to mutations in BRCA1 and BRCA2, the XRCC3(T241M) protein is proficient in homologous recombination and reverts sensitivity to mitomycin C found in XRCC3-deficient cells, whereas XRCC3(D213N) is defective in homologous recombination. Here, we report that both the XRCC3 D213N and T241M alleles are associated with an increase in centrosome number and binucleated cells. However, only the D213N allele gives an increase in spontaneous levels of apoptosis. We suggest that the inability of XRCC3 T241M to apoptotically eliminate aberrant cells with mitotic defects could increase cancer susceptibility in individuals carrying this variant. In contrast, cells carrying the XRCC3 D213N variant are able to eliminate aberrant cells by apoptosis, and consistent with this observation, this variant does not seem to be associated with cancer susceptibility.

References

Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·R S TebbsL H Thompson
Apr 24, 1997·Nature·K W Kinzler, B Vogelstein
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·L C Hsu, R L White
Jan 1, 1999·Nature·C LengauerB Vogelstein
Feb 8, 2002·Cell·Ashok R Venkitaraman
Feb 14, 2003·Carcinogenesis·John M HinzMark Meuth
Sep 18, 2004·Science·Matthew J DanielsAshok R Venkitaraman

❮ Previous
Next ❯

Citations

Nov 27, 2007·Mutation Research·G IarmarcovaiT Orsière
Mar 31, 2009·International Journal of Cancer. Journal International Du Cancer·Keke ZhouLiangfu Zhou
Aug 30, 2008·American Journal of Hematology·Lisa M Baumann Kreuziger, David P Steensma
Oct 13, 2006·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Charlotta RykSai-Mei Hou
Jul 21, 2006·Toxicology Letters·G IarmarcovaiT Orsière
Jan 30, 2009·Cell Cycle·Rachel William Anantha, James A Borowiec
Sep 19, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Qian CuiJin-Xin Bei
Jul 15, 2017·The International Journal of Biological Markers·Sílvia SoaresRui Medeiros
Jul 24, 2018·Oral Diseases·Edilmar de Moura SantosRoseana de Almeida Freitas
Apr 8, 2019·Radiation and Environmental Biophysics·Mahsa ShakeriMohammad Reza Farshidpour
Apr 14, 2018·Indian Journal of Clinical Biochemistry : IJCB·Raju Kumar Mandal, Rama Devi Mittal

❮ 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.

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

Related Papers

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Nicklas Raun JacobsenUlla Vogel
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yiping FengQingsheng Xu
© 2021 Meta ULC. All rights reserved