DOT1-like (Disruptor of telomeric silencing 1-like),
histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...
H3K79
methyltransferase
Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ross ...
(''S. cerevisiae''), also known as DOT1L, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
found in humans, as well as other eukaryotes.
The
methylation
In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
of histone H3 lysine 79 (H3K79) by DOT1L which is a conserved
epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
mark in many eukaryotic epigenomes, increases progressively along the
aging
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
process, suggesting that "DOT1L might function as a vital clock, ticking the hours impassively".
DOT1L has been reported to play an important role in the processes of
mixed-lineage leukemia (MLL)-rearranged leukemias
Small molecule inhibitors of Dot1L catalytic activity have been developed.
All three forms of H3K79 methylation (H3K79me1;
H3K79me2; H3K79me3) are catalyzed by DOT1 in yeast or DOT1L in mammals. H3K79 methylation participates in the DNA damage response and has multiple roles in nucleotide excision repair and sister chromatid recombinational repair.
References
Further reading
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