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PARP-1 and gene regulation: progress and puzzles.
W Lee Kraus1, Michael O Hottiger
1Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8511, United States.
Molecular Aspects of Medicine
|January 30, 2013
Summary
Poly(ADP-ribose) polymerase-1 (PARP-1) regulates gene transcription by modifying proteins. This review explores PARP-1's complex roles in gene regulation and therapeutic targeting.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- Poly(ADP-ribose) polymerase-1 (PARP-1), also known as ADP-ribosyltransferase Diphtheria toxin-like 1 (ARTD1), is a key nuclear protein.
- PARP-1 regulates transcription and other nuclear processes through its enzymatic activity.
Purpose of the Study:
- To review the current understanding of PARP-1's diverse roles in gene regulation.
- To explore how PARP-1 interacts with various gene regulatory pathways.
- To discuss the therapeutic potential of targeting PARP-1.
Main Methods:
- Literature review of PARP-1's function in gene regulation.
- Analysis of PARP-1's interactions with transcription machinery, chromatin modifiers, and DNA methylation.
- Review of PARP inhibitors and their effects on gene regulatory programs.
Main Results:
- PARP-1 influences gene regulation through interactions with transcription factors, coregulators, and chromatin remodeling complexes.
- PARP-1 exhibits context-specific effects on gene expression in different cell types and states.
- Chemical inhibitors targeting PARPs show promise in altering gene regulation for therapeutic benefit.
Conclusions:
- PARP-1 plays a multifaceted role in gene regulation, with context-dependent effects.
- Targeting PARP-1 with inhibitors offers potential therapeutic strategies by modulating gene regulatory programs.
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