Maintenance of genomic integrity is
essential to ensure normal organismal development and to prevent diseases such
as cancer. Nuclear DNA is packaged into chromatin, and thus genome maintenance
can be influenced by distinct chromatin environments. In particular,
post-translational modifications of histones have emerged as key regulators of
genomic integrity. Intense research during the past few years has revealed
histone H4 lysine 20 methylation (H4K20me) as critically important for the
biological processes that ensure genome integrity, such as DNA damage repair,
DNA replication and chromatin compaction. The distinct H4K20 methylation states
are mediated by SET8/PR-Set7 that catalyses monomethylation of H4K20, whereas
SUV4-20H1 and SUV4-20H2 enzymes mediate further H4K20 methylation to H4K20me2
and H4K20me3. Disruption of these H4K20-specific histone methyltransferases
leads to genomic instability, demonstrating the important functions of H4K20
methylation in genome maintenance. In this review, we explain molecular
mechanisms underlying these defects and discuss novel ideas for furthering our
understanding of genome maintenance in higher eukaryotes.
Source: H4 lysine 20 methylation: key
player in epigenetic regulation of genomic integrity. Jorgensen S, Schotta G,
Sørensen CS. Nucleic Acids Res. 2013 Mar 1;41(5):2797-806.
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