Evidence map›Paper›PMID 30597836›Full record

ArticleInternational journal of molecular sciences2018

APIM-Mediated REV3L⁻PCNA Interaction Important for Error Free TLS Over UV-Induced DNA Lesions in Human Cells.

Synnøve Brandt Ræder, Anala Nepal, Karine Øian Bjørås, Mareike Seelinger, Rønnaug Steen Kolve, Aina Nedal, Rebekka Müller, Marit Otterlei

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

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  13. Special Issue on DNA Replication Stress: Summary of Topics Covered.International journal of molecular sciences · 2019
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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

8 authors at 1 institution in 1 country.

Synnøve Brandt RæderDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. synnove.b.rader@ntnu.no.
Anala NepalDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. anala.nepal@ntnu.no.
Karine Øian BjøråsDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. karine.bjoras@ntnu.no.
Mareike SeelingerDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. mareike.seelinger@ntnu.no.
Rønnaug Steen KolveDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. ronnaugsk@gmail.com.
Aina NedalDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. ainanedal11@gmail.com.
Rebekka MüllerDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. rebrekka.muller.phd@gmail.com.
Marit OtterleiDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. marit.otterlei@ntnu.no.ORCID 0000-0002-5232-1186
Norwegian University of Science and Technology · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proliferating cell nuclear antigen (PCNA) is essential for the organization of DNA replication and the bypass of DNA lesions via translesion synthesis (TLS). TLS is mediated by specialized DNA polymerases, which all interact, directly or indirectly, with PCNA. How interactions between the TLS polymerases and PCNA affects TLS specificity and/or coordination is not fully understood. Here we show that the catalytic subunit of the essential mammalian TLS polymerase POLζ, REV3L, contains a functional AlkB homolog 2 PCNA interacting motif, APIM. APIM from REV3L fused to YFP, and full-length REV3L-YFP colocalizes with PCNA in replication foci. Colocalization of REV3L-YFP with PCNA is strongly reduced when an APIM-CFP construct is overexpressed. We also found that overexpression of full-length REV3L with mutated APIM leads to significantly altered mutation frequencies and mutation spectra, when compared to overexpression of full-length REV3L wild-type (WT) protein in multiple cell lines. Altogether, these data suggest that APIM is a functional PCNA-interacting motif in REV3L, and that the APIM-mediated PCNA interaction is important for the function and specificity of POLζ in TLS. Finally, a PCNA-targeting cell-penetrating peptide, containing APIM, reduced the mutation frequencies and changed the mutation spectra in several cell lines, suggesting that efficient TLS requires coordination mediated by interactions with PCNA.

Indexed as

DNA ReplicationProtein Interaction Domains and MotifsBiomarkersCell LineDNA-Binding ProteinsDNA DamageDNA-Directed DNA PolymeraseFluorescent Antibody TechniqueHumansMutationMutation RateProliferating Cell Nuclear AntigenProtein BindingProtein Sorting SignalsProtein TransportUltraviolet RaysBiomarkersDNA-Binding ProteinsDNA-Directed DNA PolymeraseProliferating Cell Nuclear AntigenProtein Sorting SignalsREV3L protein, humanmutagenicitymutation frequencymutations spectraPOLζSupF

Identifiers

PMID30597836
PMCPMC6337749
OpenAlexW2906836536

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.