Histone H4 Lysine 20 methylation: key player in epigenetic regulation of genomic integrity

Stine Jørgensen; Gunnar Schotta; Claus Storgaard Sørensen

doi:10.1093/nar/gkt012

Figure 2.

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Role of histone H4 HMTs during replication. (A) H4K20me1 is added during G2 and M phase and shielded from conversion until G1 phase. In preparation for the following S phase, members of the Orc complex are recruited to ORI. Part of this involves binding between Orc1 and H4K20me2. We speculate that H4K20me1 contributes to a favourable chromatin structure around the ORI that support fork progression. (B) We hypothesise that SET8 directly supports the replication fork structure, either by itself or by methylation of one or more proteins that provide structural or functional support at the fork. Loss of SET8 results in dysfunctional replication and potentially exposure of DNA structures that are targeted and cut by endonucleases, thereby generating DSBs.