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Cell. 2004 Nov 24;119(5):603-14.

Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage.

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1
The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QN, United Kingdom.

Abstract

Histone lysine methylation is a key regulator of gene expression and heterochromatin function, but little is known as to how this modification impinges on other chromatin activities. Here we demonstrate that a previously uncharacterized SET domain protein, Set9, is responsible for H4-K20 methylation in the fission yeast Schizosaccharomyces pombe. Surprisingly, H4-K20 methylation does not have any apparent role in the regulation of gene expression or heterochromatin function. Rather, we find the modification has a role in DNA damage response. Loss of Set9 activity or mutation of H4-K20 markedly impairs cell survival after genotoxic challenge and compromises the ability of cells to maintain checkpoint mediated cell cycle arrest. Genetic experiments link Set9 to Crb2, a homolog of the mammalian checkpoint protein 53BP1, and the enzyme is required for Crb2 localization to sites of DNA damage. These results argue that H4-K20 methylation functions as a "histone mark" required for the recruitment of the checkpoint protein Crb2.

PMID:
15550243
DOI:
10.1016/j.cell.2004.11.009
[Indexed for MEDLINE]
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