Figure 6.

Model of the function of LEDGF/p75 and HDGFRP2 in homologous recombination DNA repair. Repair of a DNA double strand break (DSB) by HR in active chromatin requires the histone H3K4me3- and H3K36me3-binding protein LEDGF/p75 to recruit RBBP8/CtIP and ensure efficient DNA end resection. The structurally highly similar protein HDGFRP2 binds preferentially to histone marks of silent genes (e.g. histone H3K9me3) and contributes, together with its interaction partner POGZ, to efficient DSB repair by HR. HDGFRP2 facilitates RBBP8/CtIP recruitment to the damage site and may play a role in the separate heterochromatic chromatin compartment or in chromatin silenced around the DNA DSB break. Its binding to silent chromatin may reflect its role e.g. in the inhibition of transcription and activation of Tip60 around the damage site.