Evidence map›Paper›PMID 10781066›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2000

Functional interaction between the Werner Syndrome protein and DNA polymerase delta.

A S Kamath-Loeb, E Johansson, P M Burgers, L A Loeb

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
9.4field-weighted citation impact, top 1% 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

68 citing papers in PubMed, 187 citations in OpenAlex.

  1. Review
  2. POLD3 as Controller of Replicative DNA Repair.International journal of molecular sciences · 2024
    Review
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8 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

4 authors at 2 institutions in 1 country.

A S Kamath-LoebDepartments of Pathology and Biochemistry, University of Washington, Seattle, WA 98195, USA.
E Johansson
P M Burgers
L A Loeb
Washington University in St. Louis · USUniversity of Washington · US

Funding

SPECIFICITY OF OXYGEN DNA DAMAGE AND MUTAGENESISP01AG001751 · NIA · UNIVERSITY OF WASHINGTON · PI RABINOVITCH, PETER S · 1985 to 2021
$29.6M
Tumor mutation signaturesP01CA077852 · NCI · UNIVERSITY OF WASHINGTON · PI MONNAT, RAYMOND J · 1999 to 2019
$26.0M
ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNAR01GM032431 · NIGMS · WASHINGTON UNIVERSITY · PI BURGERS, PETER M · 1985 to 2015
$6.5M
STRUCTURE/FUNCTION OF YEAST DNA POLYMERASE DELTAR01GM058534 · NIGMS · WASHINGTON UNIVERSITY · PI BURGERS, PETER M · 1999 to 2002
$499k
NCI NIH HHS CA77852NCI NIH HHS P01 CA077852NIA NIH HHS AG01751NIA NIH HHS P01 AG001751NIGMS NIH HHS GM58534NIGMS NIH HHS R01 GM032431NIGMS NIH HHS R01 GM058534
6 · The paper itself

Abstract

Werner Syndrome (WS) is an inherited disease characterized by premature onset of aging, increased cancer incidence, and genomic instability. The WS gene encodes a 1,432-amino acid polypeptide (WRN) with a central domain homologous to the RecQ family of DNA helicases. Purified WRN unwinds DNA with 3'-->5' polarity, and also possesses 3'-->5' exonuclease activity. Elucidation of the physiologic function(s) of WRN may be aided by the identification of WRN-interacting proteins. We show here that WRN functionally interacts with DNA polymerase delta (pol delta), a eukaryotic polymerase required for DNA replication and DNA repair. WRN increases the rate of nucleotide incorporation by pol delta in the absence of proliferating cell nuclear antigen (PCNA) but does not stimulate the activity of eukaryotic DNA polymerases alpha or epsilon, or a variety of other DNA polymerases. Moreover, we show that functional interaction with WRN is mediated through the third subunit of pol delta: i.e., Pol32p of Saccharomyces cerevisae, corresponding to the recently identified p66 subunit of human pol delta. Absence of the third subunit abrogates stimulation by WRN, and stimulation is restored by reconstituting the three-subunit enzyme. Our findings suggest that WRN may facilitate pol delta-mediated DNA replication and/or DNA repair and that disruption of WRN-pol delta interaction in WS cells may contribute to the previously observed S-phase defects and/or the unusual sensitivity to a limited number of DNA damaging agents.

Indexed as

DNA ReplicationBase SequenceBinding SitesDNA HelicasesDNA Polymerase IIIDNA PrimersExodeoxyribonucleasesHumansKineticsMolecular Sequence DataProliferating Cell Nuclear AntigenRecQ HelicasesTemplates, GeneticWerner SyndromeWerner Syndrome HelicaseDNA HelicasesDNA Polymerase IIIDNA PrimersExodeoxyribonucleasesProliferating Cell Nuclear AntigenRecQ HelicasesWerner Syndrome HelicaseWRN protein, human

Identifiers

PMID10781066
PMCPMC18279
OpenAlexW2008669260

What OpenQuestion holds

Textmetadata
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.