DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture.

Molecular Cancer Research : MCR
M B Kastan

Abstract

Significant progress has been made in recent years in elucidating the molecular controls of cellular responses to DNA damage in mammalian cells. Much of our understanding of the mechanisms involved in cellular DNA damage response pathways has come from studies of human cancer susceptibility syndromes that are altered in DNA damage responses. Ataxia-telangiectasia mutated (ATM), the gene mutated in the disorder ataxia-telangiectasia, codes for a protein kinase that is a central mediator of responses to DNA double-strand breaks (DSB) in cells. Once activated, ATM phosphorylates numerous substrates in the cell that modulate the response of the cell to the DNA damage. We recently developed a novel system to create DNA DSBs at defined endogenous sites in the human genome and used this system to detect protein recruitment and loss at and around these breaks by chromatin immunoprecipitation. Results from this system showed the functional importance of ATM kinase activity and phosphorylation in the response to DSBs and supported a model in which ordered chromatin structure changes that occur after DNA breakage and that depend on functional NBS1 and ATM facilitate DNA DSB repair. Insights about these pathways provide us with opportuniti...Continue Reading

References

Sep 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·M J Smerdon, M W Lieberman
May 25, 1978·The New England Journal of Medicine·R S BarM Muggeo
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S J KuerbitzM B Kastan
Jun 18, 1970·The New England Journal of Medicine·D S SchalchM H Barlow
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Apr 1, 1997·Molecular and Cellular Biology·S E MorganM B Kastan
Feb 7, 1998·Genes & Development·J D SilicianoM B Kastan
Dec 23, 1999·The Journal of Biological Chemistry·S T KimM B Kastan
Nov 21, 2000·Annals of Internal Medicine·Y Su, M Swift
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
Oct 9, 2003·The EMBO Journal·Tamar UzielYosef Shiloh
Dec 6, 2003·The EMBO Journal·Christian T CarsonMatthew D Weitzman
Jun 4, 2004·Genes & Development·Risa KitagawaMichael B Kastan
Nov 19, 2004·Nature·Michael B Kastan, Jiri Bartek
Apr 15, 2005·Nature·Vassilis G GorgoulisThanos D Halazonetis
Jun 21, 2005·Molecular and Cellular Biology·Zhongsheng YouPaul Russell
Apr 20, 2006·Nature Structural & Molecular Biology·Aude DupréJean Gautier
Jul 22, 2006·The EMBO Journal·Sergei V KozlovMartin F Lavin
Aug 15, 2006·Nature·Manuela PellegriniAndré Nussenzweig
Nov 7, 2006·Cell Metabolism·Jochen G SchneiderClay F Semenkovich
May 9, 2007·Nature Cell Biology·Elijahu BerkovichMichael B Kastan

❮ Previous
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Citations

Jun 18, 2011·Journal of Mammary Gland Biology and Neoplasia·Jay P Reddy, Yi Li
Jul 16, 2010·Cell Biochemistry and Biophysics·Ria R Ramoutar, Julia L Brumaghim
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jay P ReddyYi Li
Aug 28, 2012·Journal of Molecular Cell Biology·Mianen SunBo Xu
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Mary Ellen Perry
Jan 14, 2010·Pigment Cell & Melanoma Research·Vittoria MarescaMauro Picardo
Jan 17, 2009·Cancer Research·Terry A BeermanMary M McHugh
Nov 19, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kwanghee KimWilliam H McBride
Sep 1, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Konjeti R SekharMichael L Freeman
Jun 28, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alpna TyagiRobert A Sclafani
Mar 9, 2010·Journal of Lipid Research·Babak RazaniClay F Semenkovich
Jul 15, 2011·Clinical and Experimental Gastroenterology·Claire M PayneHarris Bernstein
Nov 26, 2013·Future Microbiology·Shiyuan Hong, Laimonis A Laimins
Mar 25, 2014·BMC Complementary and Alternative Medicine·Tengku Ahbrizal Farizal Tengku AhmadSuzana Makpol
Sep 12, 2014·Journal of the Royal Society, Interface·Luz Adriana Nicasio-CollazoEnrique Hernández-Lemus
Apr 20, 2013·Cancer Letters·Kiran Mahajan, Nupam P Mahajan
Sep 10, 2014·Nature Cell Biology·Ryotaro NishiStephen P Jackson
Nov 10, 2012·Critical Reviews in Clinical Laboratory Sciences·Zbigniew DarzynkiewiczDonald Wlodkowic
Mar 20, 2009·International Journal of Radiation Biology·Nirmal BhogalRobert G Bristow
Oct 8, 2015·Annual Review of Physiology·Anna UrygaMartin Bennett
Mar 29, 2014·Biomedical Journal·Rebecca J Boohaker, Bo Xu
Nov 26, 2014·Chemical Reviews·Eun-Kyung LimKwangyeol Lee
Nov 26, 2009·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Ingela TuressonKarl-Axel Johansson
Oct 20, 2009·European Journal of Pharmacology·Zbigniew DarzynkiewiczDonald Wlodkowic
Apr 2, 2009·Methods : a Companion to Methods in Enzymology·Ling ZhangFeng Gong
Sep 24, 2015·DNA Repair·Christopher J Bakkenist, Michael B Kastan
Dec 6, 2011·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Feb 13, 2013·Journal of Applied Toxicology : JAT·Sabry M AttiaSaleh A Bakheet
May 12, 2011·Cell Biology International·Reelma Velho-PereiraKaushala P Mishra
Oct 15, 2013·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Mayur V Jain, Marek J Łos
Dec 17, 2009·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Apr 19, 2015·Radiation Oncology·Jasmina HodzicVictor W van Beusechem

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Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.