Apoptotic DNA fragmentation factor maintains chromosome stability in a P53-independent manner

Oncogene
Bin YanC-Y Li

Abstract

DNA fragmentation factor (DFF)/caspase-activated DNase (CAD) is responsible for DNA fragmentation, a hallmark event during apoptosis. Although DNA fragmentation is an evolutionarily conserved process across species, its biological function is not clearly understood. In this study, we constructed cell lines expressing a mutant ICAD (inhibitor of CAD) protein that is resistant to caspase cleavage and therefore constantly binds to DFF/CAD and inhibits DNA fragmentation. We found that irradiation of these cells led to increased chromosome aberrations and aneuploidy when compared with their parental controls. The increased chromosome instability is observed irrespective of cellular P53 status, suggesting that the effect of DFF/CAD is independent of P53. Inhibition of apoptotic DNA fragmentation resulted in increased clonogenic survival of irradiated cells and a delay in removal of cells with DNA damages induced by radiation, an effect similar to that in cells with p53 mutations. Consistent with DFF/CAD's effect on clonogenic survival, tumors established from cells deficient in DNA fragmentation showed enhanced growth in nude mice. Therefore, our results suggest that DFF/CAD plays an important and P53-independent role in maintaining ...Continue Reading

References

Mar 1, 1990·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·P F Wheat, R C Spencer
Feb 15, 1986·Cancer Genetics and Cytogenetics·D W Yandell, J B Little
Aug 1, 1986·Annals of Neurology·B W LittleD C Gajdusek
Jun 1, 1982·Mutation Research·H L Liber, W G Thilly
Jan 25, 1996·The New England Journal of Medicine·H CaronR Versteeg
Aug 1, 1996·Human Gene Therapy·T M Kinsella, G P Nolan
Aug 1, 1996·Genes, Chromosomes & Cancer·M SchwabL C Amler
Oct 1, 1996·Trends in Genetics : TIG·K Nasmyth
Feb 7, 1997·Cell·A G PaulovichL H Hartwell
Apr 10, 1997·Nature·C LengauerB Vogelstein
Jul 11, 1998·Molecular Cell·H HermekingB Vogelstein
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·N MukaeS Nagata
Aug 26, 1998·Genes, Chromosomes & Cancer·M Van GeleF Speleman
Jan 1, 1999·Nature·C LengauerB Vogelstein
Jul 26, 2000·The Journal of Cell Biology·D LechardeurG L Lukacs
Jan 14, 2003·Nature Immunology·Kohki KawaneShigekazu Nagata
Mar 26, 2003·Cell Death and Differentiation·S NagataH Fukuyama
Sep 5, 2003·The Journal of Biological Chemistry·Bin YanMichael Lilly
Jun 11, 2005·Trends in Genetics : TIG·Yoshinori Watanabe
Jan 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bin YanChuan-Yuan Li

❮ Previous
Next ❯

Citations

Jun 23, 2009·Carcinogenesis·Bin YanChuan-Yuan Li
Jul 15, 2011·Clinical and Experimental Gastroenterology·Claire M PayneHarris Bernstein
May 25, 2010·Biochemical and Biophysical Research Communications·Lars Holmgren
Nov 4, 2015·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Fatemeh BagheriNader Sheibani
Nov 20, 2016·The FEBS Journal·Brian D Larsen, Claus S Sørensen

❮ Previous
Next ❯

Related Concepts

Related Feeds

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

Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Discover the latest research on ALPS here.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Bin YanChuan-Yuan Li
Proceedings of the National Academy of Sciences of the United States of America
A BergsmedhL Holmgren
© 2022 Meta ULC. All rights reserved