Evidence map›Paper›PMID 33940558›Full record

ReviewDNA repair2021

PARP1: Structural insights and pharmacological targets for inhibition.

Jacob O Spiegel, Bennett Van Houten, Jacob D Durrant

Open access · hybridAbstract readReview
In one paragraph

Review in DNA repair, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 91 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. The first and second zinc finger domains from Poly-ADP-ribose polymerase 1 (PARP1) are modified by hydrogen sulfide.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026
    Article
  5. Article
  6. Cancer-associated TRF1 mutations alter PARP1 interaction dynamics: an in silico study.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Experimental and Mechanistic Validation of PARP1pred for Identifying Potent Leads.Computational and structural biotechnology journal · 2026
    Article
  13. Article
  14. Dynamic Assemblies in Genome Maintenance.Advances in experimental medicine and biology · 2026
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Jacob O SpiegelDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Bennett Van HoutenUPMC-Hillman Cancer Center, Pittsburgh, PA, 15232, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Jacob D DurrantDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA. Electronic address: durrantj@pitt.edu.
University of Pittsburgh · US

Funding

Watching cooperative interactions between base and nucleotide excision repair proteinsR35ES031638 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Bennett Van Houten · 2020 to 2026
$6.2M
NIEHS NIH HHS R35 ES031638
6 · The paper itself

Abstract

Poly(ADP-ribose) polymerase 1 (PARP1, also known as ADPRT1) is a multifunctional human ADP-ribosyltransferase. It plays a role in multiple DNA repair pathways, including the base excision repair (BER), non-homologous end joining (NHEJ), homologous recombination (HR), and Okazaki-fragment processing pathways. In response to DNA strand breaks, PARP1 covalently attaches ADP-ribose moieties to arginine, glutamate, aspartate, cysteine, lysine, and serine acceptor sites on both itself and other proteins. This signal recruits DNA repair proteins to the site of DNA damage. PARP1 binding to these sites enhances ADP-ribosylation via allosteric communication between the distant DNA binding and catalytic domains. In this review, we provide a general overview of PARP1 and emphasize novel potential approaches for pharmacological inhibition. Clinical PARP1 inhibitors bind the catalytic pocket, where they directly interfere with ADP-ribosylation. Some inhibitors may further enhance potency by "trapping" PARP1 on DNA via an allosteric mechanism, though this proposed mode of action remains controversial. PARP1 inhibitors are used clinically to treat some cancers, but resistance is common, so novel pharmacological approaches are urgently needed. One approach may be to design novel small molecules that bind at inter-domain interfaces that are essential for PARP1 allostery. To illustrate these points, this review also includes instructive videos showing PARP1 structures and mechanisms.

Indexed as

DNA RepairDNADNA DamageDrug Resistance, NeoplasmHumansNeoplasmsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsProtein ConformationDNAPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsCancerChemotherapyDNA repairDrug resistancePARP1Review

Identifiers

PMID33940558
PMCPMC8206044
OpenAlexW3155228050

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.