WHSC1 (MMSET) histone methyltransferase dimethylates histone H4 (HIST1H4A) on lysine residue K21 (commonly labeled in literature as K20), locally increasing the concentration of the H4K20Me2 mark. H4K20Me2 (Me2-K21-HIST1H4A) serves as a binding site for TP53BP1 (53BP1). The recruitment of WHSC1 to DNA double-strand breaks (DSBs) is independent of RNF8 and RNF168, but the catalytic activity of all three proteins is necessary for binding and accumulation of TP53BP1 at DSBs (Pei et al. 2011).
histone methyltransferase activity (H4-K20 specific) of DNA DSBs:p-MRN:p-S1981,Ac-K3016-ATM:KAT5:p-S139-H2AFX-Nucleosome:p-5T-MDC1:p-S102-WHSC1 [nucleoplasm]