Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair

Ayako Ui, Yuko Nagaura, Akira Yasui

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)468-482
Number of pages15
JournalMolecular Cell
Volume58
Issue number3
DOIs
Publication statusPublished - 2015 May 7

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair'. Together they form a unique fingerprint.

Cite this