Transcriptional Elongation Factor ENL Phosphorylated by ATM Recruits Polycomb and Switches Off Transcription for DSB Repair
Copyright policy )Transcriptional Elongation Factor ENL Phosphorylated by ATM Recruits Polycomb and Switches Off Transcription for DSB Repair
Transcription is repressed if a DNA double-strand break (DSB) is introduced in close proximity to a transcriptional activation site at least in part by H2A-ubiquitination. While ATM signaling is involved, how it controls H2A-ubiquitination remains unclear. Here, we identify that, in response to DSBs, a transcriptional elongation factor, ENL (MLLT1), is phosphorylated by ATM at conserved SQ sites. This phosphorylation increases the interaction between ENL and the E3-ubiquitin-ligase complex of Polycomb Repressive Complex 1 (PRC1) via BMI1. This interaction promotes enrichment of PRC1 at transcription elongation sites near DSBs to ubiquitinate H2A leading to transcriptional repression. ENL SQ sites and BMI1 are necessary for KU70 accumulation at DSBs near active transcription sites and cellular resistance to DSBs. Our data suggest that ATM-dependent phosphorylation of ENL functions as switch from elongation to Polycomb-mediated repression to preserve genome integrity.
- Tohoku University Japan
DNA Repair, Transcription, Genetic, Blotting, Western, Molecular Sequence Data, Ataxia Telangiectasia Mutated Proteins, Cell Line, Tumor, Humans, DNA Breaks, Double-Stranded, Amino Acid Sequence, Phosphorylation, Molecular Biology, Polycomb Repressive Complex 1, Microscopy, Confocal, Sequence Homology, Amino Acid, Nuclear Proteins, Cell Biology, Neoplasm Proteins, Luminescent Proteins, HEK293 Cells, RNA Interference, Protein Binding, Transcription Factors
DNA Repair, Transcription, Genetic, Blotting, Western, Molecular Sequence Data, Ataxia Telangiectasia Mutated Proteins, Cell Line, Tumor, Humans, DNA Breaks, Double-Stranded, Amino Acid Sequence, Phosphorylation, Molecular Biology, Polycomb Repressive Complex 1, Microscopy, Confocal, Sequence Homology, Amino Acid, Nuclear Proteins, Cell Biology, Neoplasm Proteins, Luminescent Proteins, HEK293 Cells, RNA Interference, Protein Binding, Transcription Factors
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