H4K20me2: Orchestrating the recruitment of DNA repair factors in nucleotide excision repair.

The integrity of the genome is maintained by specific DNA repair pathways. The main pathway removing DNA lesions induced by exposure to UV light is nucleotide excision repair (NER). The DNA damage response at chromatin is accompanied by the recruitment of DNA repair factors to the lesion site and the deposition of specific histone marks. The function of these histone marks in NER stays for the most part elusive. We have recently reported that the methyltransferase MMSET catalyzes the dimethylation of histone H4 at lysine 20 (H4K20me2) at the lesion site. The deposition of H4K20me2 at DNA damage sites elicits the recruitment of the NER factor XPA providing evidence for an H4K20me2-dependent DNA repair factor recruitment mechanism during lesion recognition in the global-genomic branch of NER. Here we discuss how H4K20me2 might impact on the chromatin conformation and the DNA damage response.