Figure 5. SIRT6 prevents collision between transcription and DSB repair machineries. Under basal conditions KDM2A demethylates H3K36 at transcription start site. Upon DNA damage SIRT6, is recruited to the DSB locus and mono-ADP ribosylates KDM2A leading to its displacement from chromatin. This leads to accumulation of H3K36me2 marks around the DSB site, which recruits HP1α and promotes deposition of H3K9me3 mark leading to local chromatin compaction. As a result, transcription is paused and DNA repair by NHEJ ensues.