Evidence map›Paper›PMID 34795260›Full record

ArticleNature communications2021

HPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADP-ribose modifications.

Marie-France Langelier, Ramya Billur, Aleksandr Sverzhinsky, Ben E Black, John M Pascal

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.6field-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

47 citing papers in PubMed, 69 citations in OpenAlex.

  1. Review
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  3. Cryo-EM structure of ALC1 in an open conformation bound to a PARylated nucleosome.Acta crystallographica. Section D, Structural biology · 2026
    Article
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  8. A Population-Specific PARP1 Gene Variation Modulates PARP Trapping.bioRxiv : the preprint server for biology · 2025
    Article
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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

5 authors at 2 institutions in 2 countries.

Marie-France LangelierDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, H3C 3J7, Canada.
Ramya BillurDepartment of Biochemistry and Biophysics, Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6059, USA.ORCID http://orcid.org/0000-0002-8677-0801
Aleksandr SverzhinskyDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, H3C 3J7, Canada.ORCID http://orcid.org/0000-0003-1405-925X
Ben E BlackDepartment of Biochemistry and Biophysics, Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6059, USA.
John M PascalDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, H3C 3J7, Canada. john.pascal@umontreal.ca.ORCID http://orcid.org/0000-0002-2714-4317
Université de Montréal · CAUniversity of Pennsylvania · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Centromere identity, strength, and regulationR35GM130302 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Ben E. Black · 2019 to 2026
$4.3M
CIHR PJT173370NCI NIH HHS P01 CA092584NIGMS NIH HHS R35 GM130302
6 · The paper itself

Abstract

PARP1 and PARP2 produce poly(ADP-ribose) in response to DNA breaks. HPF1 regulates PARP1/2 catalytic output, most notably permitting serine modification with ADP-ribose. However, PARP1 is substantially more abundant in cells than HPF1, challenging whether HPF1 can pervasively modulate PARP1. Here, we show biochemically that HPF1 efficiently regulates PARP1/2 catalytic output at sub-stoichiometric ratios matching their relative cellular abundances. HPF1 rapidly associates/dissociates from multiple PARP1 molecules, initiating serine modification before modification initiates on glutamate/aspartate, and accelerating initiation to be more comparable to elongation reactions forming poly(ADP-ribose). This "hit and run" mechanism ensures HPF1 contributions to PARP1/2 during initiation do not persist and interfere with PAR chain elongation. We provide structural insights into HPF1/PARP1 assembled on a DNA break, and assess HPF1 impact on PARP1 retention on DNA. Our data support the prevalence of serine-ADP-ribose modification in cells and the efficiency of serine-ADP-ribose modification required for an acute DNA damage response.

Indexed as

ADP-RibosylationDNA DamageAdenosine Diphosphate RiboseBlotting, WesternCarrier ProteinsDNADNA Breaks, Double-StrandedHumansMutationNuclear ProteinsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesProtein BindingAdenosine Diphosphate RiboseCarrier ProteinsDNAHPF1 protein, humanNuclear ProteinsPARP1 protein, humanPARP2 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerases

Identifiers

PMID34795260
PMCPMC8602370
OpenAlexW3212892569

What OpenQuestion holds

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LicenceCC BY
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.