TY - JOUR
T1 - Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair
AU - Ui, Ayako
AU - Nagaura, Yuko
AU - Yasui, Akira
N1 - Funding Information:
We thank Dr. Shirley McCready for editing the text. We thank Dr. Atsushi Shibata for discussions. We also thank Dr. Yuuki Murakami for technical assistance and Drs. Susan Janicki and Maria Jasin for experimental material. This work was funded by the Grants-in-Aid for Scientific Research and from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, to A.Y. (24310037 and 22131005) and to A.U. (22131006).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/7
Y1 - 2015/5/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2015.03.023
DO - 10.1016/j.molcel.2015.03.023
M3 - Article
C2 - 25921070
AN - SCOPUS:84928907539
SN - 1097-2765
VL - 58
SP - 468
EP - 482
JO - Molecular Cell
JF - Molecular Cell
IS - 3
ER -