gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes

DNA Repair
Manuel Stucki, Stephen P Jackson

Abstract

Higher-order chromatin structure presents a barrier to the recognition and repair of DNA lesions. Thus, cells must be equipped with mechanisms to surpass this natural obstacle. DNA damage induces histone H2AX phosphorylation by the phosphoinositide 3-kinase like kinases ATM, ATR and DNA-PKcs. H2AX phosphorylation contributes to DNA double-strand break repair but the mechanisms involved are not yet fully understood. In this review, we discuss recent advances in our understanding of how cells use the epigenetic mark of H2AX phosphorylation to dynamically link the DNA-damage-response machinery to broken chromosomes. In addition, we highlight potential regulatory mechanisms of H2AX phosphorylation and speculate about a central functional role of this post-translational histone modification at the interface of DNA repair, chromatin-structure modulation and cell-cycle checkpoint activation.

References

Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Mar 21, 2001·Nature Reviews. Genetics·D C van GentR Kanaar
Sep 26, 2001·The Journal of Biological Chemistry·S BurmaD J Chen
Jan 5, 2002·Molecular and Cellular Biology·Kazuhiko YamaneJunjie Chen
Apr 6, 2002·Science·Arkady CelesteAndré Nussenzweig
May 30, 2002·Proceedings of the National Academy of Sciences of the United States of America·Craig H BassingFrederick W Alt
Jul 27, 2002·Science·John Rouse, Stephen P Jackson
Nov 26, 2002·Nature Cell Biology·Oscar Fernandez-CapetilloAndré Nussenzweig
Feb 28, 2003·Nature·Michal GoldbergStephen P Jackson
Feb 28, 2003·Nature·Grant S StewartStephen J Elledge
Apr 17, 2003·The Journal of Biological Chemistry·Irene M WardJunjie Chen
May 23, 2003·Cold Spring Harbor Symposia on Quantitative Biology·D DurocherS P Jackson
Jun 7, 2003·Nature Cell Biology·Arkady CelesteAndré Nussenzweig
Jun 26, 2003·The Journal of Biological Chemistry·Kuniyoshi IwabuchiAidan J Doherty
Aug 14, 2003·Cell·Arkady CelesteAndré Nussenzweig
Sep 10, 2003·Cell Cycle·Oscar Fernandez-CapetilloAndré Nussenzweig
Oct 25, 2003·Science·Isaac A MankeMichael B Yaffe
Oct 25, 2003·Science·Xiaochun YuJunjie Chen
Oct 28, 2003·The Journal of Biological Chemistry·Maria RodriguezZhou Songyang
Jan 9, 2004·Cell Cycle·Craig H Bassing, Frederick W Alt
Jan 27, 2004·The Journal of Biological Chemistry·Irene M WardJunjie Chen
May 11, 2004·Nature Structural & Molecular Biology·Julie A ClappertonStephen J Smerdon
May 11, 2004·Nature Structural & Molecular Biology·R Scott WilliamsJ N Mark Glover
Jun 29, 2004·The Journal of Biological Chemistry·Xingzhi XuDavid F Stern
Jul 10, 2004·Structure·Maria Victoria E BotuyanGeorges Mer
Jul 29, 2004·DNA Repair·Craig H Bassing, Frederick W Alt
Jul 29, 2004·DNA Repair·Manuel Stucki, Stephen P Jackson
Sep 21, 2004·The Journal of Biological Chemistry·Zhenkun LouJunjie Chen
Oct 1, 2004·The Journal of Biological Chemistry·Paul A JowseyJohn Rouse
Oct 27, 2004·Trends in Biochemical Sciences·J N Mark GloverMegan S Lee
Nov 5, 2004·Nature·Yentram HuyenThanos D Halazonetis
Dec 22, 2004·Molecular Cell·Anyong XieRalph Scully

❮ Previous
Next ❯

Citations

Aug 15, 2013·Archives of Dermatological Research·Jee-Youn KimSun Lee
Mar 13, 2010·Chromosoma·Stephanie Jungmichel, Manuel Stucki
Aug 21, 2007·Current Oncology Reports·Deepa Sampath, William Plunkett
Sep 17, 2011·Journal of Molecular Neuroscience : MN·Michal KirshnerAri Barzilai
Jun 17, 2010·Molecular Neurobiology·Andrew H Wyllie
May 22, 2009·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Tomohiko OhtaMamoru Fukuda
Aug 7, 2013·Mutation Research·Ralph Scully, Anyong Xie
Aug 11, 2010·Journal of Proteome Research·Kristin E CanoYuan Chen
Jan 1, 2010·Cell Death & Disease·V MeltserY Shaul
Dec 25, 2007·Cell Research·Meena ShrivastavJac A Nickoloff
Oct 22, 2008·Nature·Simone DifilippantonioAndré Nussenzweig
Mar 27, 2007·Nature Cell Biology·Spencer J CollisSimon J Boulton
Oct 24, 2007·Nature Cell Biology·Zhongsheng YouTony Hunter
Dec 23, 2008·Nature Cell Biology·Kuntian LuoZhenkun Lou
Feb 5, 2011·Nature Protocols·Keiji SuzukiShunichi Yamashita
Nov 14, 2008·Nature Reviews. Cancer·William M BonnerYves Pommier
Feb 21, 2008·Nature Reviews. Molecular Cell Biology·Dana Branzei, Marco Foiani
Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Jan 16, 2009·Nature Reviews. Neuroscience·Peter J McKinnon
Apr 21, 2009·Nature Structural & Molecular Biology·Ashish LalDipanjan Chowdhury
Jul 28, 2009·Nature Structural & Molecular Biology·Anyong XieRalph Scully
Aug 31, 2010·Nature Structural & Molecular Biology·Kyle M MillerStephen P Jackson
Dec 6, 2012·Nature Structural & Molecular Biology·Catherine A MusselmanTatiana G Kutateladze
Jan 8, 2008·Nature Structural & Molecular Biology·Eric J Bennett, J Wade Harper
May 8, 2008·Nature Structural & Molecular Biology·Jiri Lukas, Jiri Bartek
Dec 11, 2007·Oncogene·E R Phillips, P J McKinnon
Aug 31, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ali JavaheriStephen J Kron
Mar 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ruani N FernandoPatrik Ernfors
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ildiko HajduStephen J Elledge
May 6, 2009·The Journal of Biological Chemistry·Jiaxue WuXiaochun Yu
Feb 2, 2010·The Journal of Biological Chemistry·Sung-Hwan MoonLawrence A Donehower
Aug 24, 2010·The Journal of Biological Chemistry·S Mehdi BelgnaouiO John Semmes
Mar 21, 2012·The Journal of Biological Chemistry·Meyke Ausman KangToru Ouchi
May 9, 2007·The Journal of Experimental Medicine·Simone DifilippantonioAndré Nussenzweig
Sep 6, 2008·Nucleic Acids Research·Andrea KinnerGeorge Iliakis
Feb 21, 2009·Nucleic Acids Research·Kenji WatanabeSatoshi Tateishi
Apr 14, 2010·Nucleic Acids Research·Keiji SuzukiShunichi Yamashita
Feb 10, 2012·Nucleic Acids Research·Charles VadnaisAlain Nepveu
Nov 15, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Ashwin KotnisQiang Pan-Hammarström
Dec 13, 2006·Genes & Development·Nadya Dimitrova, Titia de Lange

❮ 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.

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.