Nabieh Ayoub
Technion - Israel Institute of Technology, Israel
Double-strand breaks (DSBs) trigger rapid and transient transcription pause to prevent collisions between repair and transcription machineries at damage sites. Little is known about the mechanisms that ensure transcription block after DNA damage. Here we reveal a novel role of the negative elongation factor, NELF, in blocking transcription activity nearby DSBs. We show that NELF-E and NELF-A are rapidly recruited to DSB sites. Furthermore, NELF-E recruitment and its repressive activity are both required for switching off transcription at DSBs. Remarkably, using I-Sce-I endonuclease and CRISPR-Cas9 systems, we observed that NELF-E is preferentially recruited, in a PARP1-dependent manner, to DSBs induced upstream transcriptionally active rather than inactive genes. Moreover, the presence of RNA polymerase II is a prerequisite for the preferential recruitment of NELF-E to DNA breakage sites. Additionally, we demonstrate that NELF-E is required for intact repair of DSBs. Altogether, our data identified NELF complex as a new component in the DNA damage response.
Nabieh Ayoub began his scientific career at the Hebrew University (1989-1993) where he received a BSc in Biology. He has done his Master’s degree with distinction in Genetics (1994-1996) studying chromosome X inactivation. Supported by the Levy Eshkool Fellowship from the Israeli Ministry of Science, he pursued his PhD in the study of heterochromatic gene regulation under the supervision of Professor Amikam Cohen at Hadassah Medical School, the Hebrew University (1997-2002). He is an Assistant Professor at the Israel Institute of Technology – Technion. In 2016, he was prompted to the degree of Associate Professor with tenure.
Email: ayoubn@technion.ac.il
