Inherited or acquired defects in detecting, signalling or repairing DNA damage are associated with various human pathologies, including immunodeficiencies, neurodegenerative diseases and various forms of cancer. Nuclear DNA is packaged into chromatin and therefore the true in vivo substrate of damaged DNA occurs within the context of chromatin. Our work aims to decipher the mechanisms by which cells detect DNA damage and signal its presence to the DNA-repair and cell-cycle machineries. In particular, much of our work has focused on DNA DSBs (double-strand breaks) that are generated by ionizing radiation and radiomimetic chemicals, and which can also arise when the DNA replication apparatus encounters other DNA lesions. In the present review, we describe some of our recent work, as well as the work of other laboratories, that has identified new chromatin proteins that mediate DSB responses, control SDB processing or modulate chromatin structure at DNA-damage sites. We also aim to survey several recent advances in the field that have contributed to our understanding of how particular histone modifications and involved in DNA repair. It is our hope that by understanding the role of chromatin and its modifications in promoting DNA repair and genome stability, this knowledge will provide opportunities for developing novel classes of drugs to treat human diseases, including cancer.
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April 2012
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Conference Article|
March 21 2012
Histone marks: repairing DNA breaks within the context of chromatin
Kyle M. Miller;
1The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, U.K., and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
2Correspondence may be addressed to either author (emailkyle.miller@mail.utexas.edu or s.jackson@gurdon.cam.ac.uk).
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Stephen P. Jackson
Stephen P. Jackson
2
1The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, U.K., and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
2Correspondence may be addressed to either author (emailkyle.miller@mail.utexas.edu or s.jackson@gurdon.cam.ac.uk).
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Publisher: Portland Press Ltd
Received:
October 07 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (2): 370–376.
Article history
Received:
October 07 2011
Citation
Kyle M. Miller, Stephen P. Jackson; Histone marks: repairing DNA breaks within the context of chromatin. Biochem Soc Trans 1 April 2012; 40 (2): 370–376. doi: https://doi.org/10.1042/BST20110747
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