Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast

Molecular and Cellular Biology
Toru M NakamuraPaul Russell

Abstract

Mammalian ATR and ATM checkpoint kinases modulate chromatin structures near DNA breaks by phosphorylating a serine residue in the carboxy-terminal tail SQE motif of histone H2AX. Histone H2A is similarly regulated in Saccharomyces cerevisiae. The phosphorylated forms of H2AX and H2A, known as gamma-H2AX and gamma-H2A, are thought to be important for DNA repair, although their evolutionarily conserved roles are unknown. Here, we investigate gamma-H2A in the fission yeast Schizosaccharomyces pombe. We show that formation of gamma-H2A redundantly requires the ATR/ATM-related kinases Rad3 and Tel1. Mutation of the SQE motif to AQE (H2A-AQE) in the two histone H2A genes caused sensitivity to a wide range of genotoxic agents, increased spontaneous DNA damage, and impaired checkpoint maintenance. The H2A-AQE mutations displayed a striking synergistic interaction with rad22Delta (Rad52 homolog) in ionizing radiation (IR) survival. These phenotypes correlated with defective phosphorylation of the checkpoint proteins Crb2 and Chk1 and a failure to recruit large amounts of Crb2 to damaged DNA. Surprisingly, the H2A-AQE mutations substantially suppressed the IR hypersensitivity of crb2Delta cells by a mechanism that required the RecQ-like ...Continue Reading

References

Sep 25, 1993·Nucleic Acids Research·D F MurisA Pastink
Dec 19, 1998·The EMBO Journal·R G MartinhoN J Bentley
Jan 23, 1999·Current Opinion in Cell Biology·N Rhind, P Russell
Apr 24, 1999·Biochimie·T Caspari, A M Carr
Jan 19, 2000·Molecular Biology of the Cell·B A Baber-FurnariP Russell
May 29, 2000·Molecular and Cellular Biology·B A MoserP Russell
Dec 6, 2000·Mutation Research· van den Bosch MA Pastink
Jan 5, 2001·Nature·J A DownsS P Jackson
Mar 10, 2001·Molecular and Cellular Biology·N Rhind, P Russell
Apr 21, 2001·Molecular and Cellular Biology·M KaiT S Wang
Jun 30, 2001·Molecular Cell·T UsuiJ H Petrini
Aug 11, 2001·Science·T Jenuwein, C D Allis
Sep 7, 2001·Genes & Development·D D'Amours, S P Jackson
Nov 21, 2001·Nature Cell Biology·A A AlcasabasS J Elledge
Nov 21, 2001·Nature Cell Biology·K Tanaka, P Russell
Feb 21, 2002·Molecular Biology of the Cell·Tom D Wolkow, Tamar Enoch
Mar 14, 2002·Current Opinion in Cell Biology·Justine Melo, David Toczyski
Mar 15, 2002·Current Opinion in Genetics & Development·Christophe RedonWilliam Bonner
Apr 6, 2002·Science·Arkady CelesteAndré Nussenzweig
May 23, 2002·Genes & Development·Thomas CaspariAntony M Carr
May 30, 2002·Proceedings of the National Academy of Sciences of the United States of America·Craig H BassingFrederick W Alt
Sep 28, 2002·Nature·Alexander W BirdMichael F Christman
Nov 6, 2002·Molecular and Cellular Biology·Song Qin, Mark R Parthun
Nov 7, 2002·Current Biology : CB·Junya KobayashiKenshi Komatsu
Nov 26, 2002·Nature Cell Biology·Oscar Fernandez-CapetilloAndré Nussenzweig

❮ Previous
Next ❯

Citations

May 18, 2005·DNA Repair·Valerie GarciaAntony M Carr
Jul 26, 2011·Asian Journal of Andrology·Godfried W van der HeijdenWilly M Baarends
Sep 11, 2010·Nature·Tiago CarneiroMiguel Godinho Ferreira
Jun 14, 2013·Nature·Amélie Fradet-TurcotteDaniel Durocher
Sep 17, 2005·Nature Reviews. Molecular Cell Biology·Haico van Attikum, Susan M Gasser
May 9, 2009·Nature Reviews. Molecular Cell Biology·Ashby J Morrison, Xuetong Shen
May 13, 2011·The Journal of Biological Chemistry·Ming YueYong-jie Xu
Oct 2, 2008·The Journal of Biological Chemistry·Nikole T GreesonSteven L Sanders
Apr 10, 2009·The Journal of Biological Chemistry·Yong-Jie Xu, Thomas J Kelly
Feb 4, 2005·Molecular Biology of the Cell·Daniel G Pankratz, Susan L Forsburg
Feb 3, 2012·Molecular Biology of the Cell·Theresa J Berens, David P Toczyski
Oct 20, 2012·Nucleic Acids Research·Oliver LimboPaul Russell
Nov 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Petra Langerak, Paul Russell
Mar 3, 2011·Genes & Development·Sophie E Polo, Stephen P Jackson
Jun 17, 2009·Molecular and Cellular Biology·Emily A OutwinMatthew J O'Connell
Dec 10, 2008·Molecular and Cellular Biology·Omar ZgheibThanos D Halazonetis
Oct 10, 2012·Molecular and Cellular Biology·Sarah A SabatinosSusan L Forsburg
Aug 29, 2012·Molecular and Cellular Biology·Arancha SánchezPaul Russell
Jan 30, 2013·Molecular and Cellular Biology·Si Young LeePaul Russell
Jan 24, 2007·Molecular and Cellular Biology·Xiaoyuan SongMartin A Gorovsky
Aug 29, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Jeffrey FillinghamNevan J Krogan
Feb 24, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Stephen E HumpalJocelyn E Krebs
Jun 30, 2006·Annual Review of Genetics·Jacob C Harrison, James E Haber
Feb 4, 2009·Cytogenetic and Genome Research·S MisriT K Pandita
Sep 2, 2006·Cell Division·Melissa M Adams, Phillip B Carpenter

❮ Previous
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