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up in Epigenetics & Proteomics #2
tumor suppressor role for H4K20me0 recognition?
The proteins TONSL (Tonsoku-like,
a DNA repair protein)
and MMS22L (methyl methanesulfonate-sensitivity protein 22-like,
repair protein) form a complex known to be necessary for replication
stability and repair of replication-associated DNA damage. The
complex was already shown to associate with soluble (non-nucleosomal) histones
chaperone ASF1 and MCM2
(a histone-binding domain). In their recent article published in Nature,
et al. bring
evidence that the
TONSL-MMS22L complex also interacts with nucleosomal
histones in chromatin.
et al. showed that the ARD (ankyrin repeat
domain) of TONSL
recognizes and reads histone H4 tails only when they are
unmethylated at lysine 20 (H4K20me0).
TONSL recruitment to replication forks and post-replicative chromatin,
to late G2/M phase chromatin, is favored by ARD recognition of H4K20me0
binding to H4K20me0 is
very likely to be required for TONSL presence at damaged forks and DNA
which strongly places H4K20me0 as a central player in TONSL-MMS22L
stability functions. The authors propose H4K20me0 as a histone
signature for post-replicative chromatin, further highlighting the link
DNA repair and the replication state of a genomic locus.
Since multiple TONSL
ARD mutations are reported in cancer, this study brings new insights in
tumor suppressor function of H4K20me0 recognition and its strong
being explored as a new cancer therapy target.
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