Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation

Author:

Gibson Bryan A.1,Zhang Yajie2,Jiang Hong3,Hussey Kristine M.4,Shrimp Jonathan H.3,Lin Hening3,Schwede Frank5,Yu Yonghao2,Kraus W. Lee1

Affiliation:

1. The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences and The Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

2. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

3. Howard Hughes Medical Institute and Department of Chemistry, Cornell University, Ithaca, NY 14850, USA.

4. Sarepta Therapeutics, Cambridge, MA 02142, USA.

5. Biolog Life Science Institute, D-28199 Bremen, Germany.

Abstract

Mapping ADP-ribosylation by PARPs During many cell processes, ADP-ribose is transferred from NAD + onto protein substrates by poly(ADP-ribose) polymerases (PARPs). Gibson et al. developed a method to track ribose transfer events and mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome and genome. One PARP-1 target is NELF, a protein complex that regulates pausing by RNA polymerase II. If NELF is ribosylated, pausing is released and productive transcription elongation resumes. Science , this issue p. 45

Funder

American Heart Association

Cancer Prevention and Research Institute of Texas

Welch Foundation

UT Southwestern Endowed Scholars Program

NIH National Institute of General Medical Sciences

NIH National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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