The DNA damage response protein 53BP1 utilizes its tandem tudor domain to recognize dimethylated lysine 20 on histone (H4K20me2), a modification associated with double-strand DNA breaks. UNC-2170, identified by screening, was found to be a micro M ligand for 53BP1 which also demonstrated at least 17-fold selectivity for 53BP1 over other methyl-lysine binding proteins. The compound functions as a 53BP1 antagonist in cell lysates and suppresses class switch recombination in whole cells, a process requiring a functioning 53BP1 tudor domain1.
References:
1. MT Perfetti et al. ACS Chem. Biol. 2015 10:1072
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