Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage.
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.
Mesh Terms:
Cell Cycle Proteins, Cell Survival, DNA Damage, Gene Expression Regulation, Fungal, Genes, cdc, Histone-Lysine N-Methyltransferase, Histones, Intracellular Signaling Peptides and Proteins, Lysine, Methylation, Mutation, Nuclear Proteins, Phosphoproteins, Protein Methyltransferases, Protein Transport, Schizosaccharomyces, Schizosaccharomyces pombe Proteins
Cell Cycle Proteins, Cell Survival, DNA Damage, Gene Expression Regulation, Fungal, Genes, cdc, Histone-Lysine N-Methyltransferase, Histones, Intracellular Signaling Peptides and Proteins, Lysine, Methylation, Mutation, Nuclear Proteins, Phosphoproteins, Protein Methyltransferases, Protein Transport, Schizosaccharomyces, Schizosaccharomyces pombe Proteins
Cell
Date: Nov. 24, 2004
PubMed ID: 15550243
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