Evidence map›Paper›PMID 40042814›Full record

ArticleNucleic acids research2025

Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps.

Anna Karlowicz, Andrzej B Dubiel, Marta Wyszkowska, Kazi Amirul Hossain, Jacek Czub, Michal R Szymanski

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. 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

6 authors.

Anna KarlowiczStructural Biology Laboratory, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.ORCID 0000-0002-6940-8210
Andrzej B DubielStructural Biology Laboratory, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.ORCID 0000-0002-2743-5122
Marta WyszkowskaStructural Biology Laboratory, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.ORCID 0000-0003-4800-0600
Kazi Amirul HossainDepartment of Physical Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.ORCID 0000-0002-1149-964X
Jacek CzubDepartment of Physical Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.ORCID 0000-0003-3639-6935
Michal R SzymanskiStructural Biology Laboratory, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.ORCID 0000-0001-9452-8508

Funding

ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
EMBO 4129European Regional Development Fund POIR.04.04.00-00-3E44/17-00European Research Council 852662NIGMS NIH HHS R01 GM129325University of Gdansk
6 · The paper itself

Abstract

Single-stranded DNA (ssDNA) is an important intermediate generated during various cellular DNA transactions, primarily during long-patch base excision repair. When displaced by DNA polymerase during strand displacement DNA synthesis, ssDNA forms 5' overhangs (flaps) that are either cleaved by DNA nucleases or protected from degradation upon binding of single-stranded DNA-binding proteins (SSB). Several nucleases are involved in the removal of ssDNA flaps in human mitochondria, namely the endonucleases FEN1 and DNA2, as well as the exonuclease MGME1. In this study, we show that another mitochondrial nuclease, EXOG, cleaves DNA flaps in both free and SSB-protected forms. We established that the presence of the Wing domain in EXOG structure provides additional binding site for ssDNA and 5' flaps irrespective of monovalent salt concentration. Importantly, DNA flap cleavage by EXOG is compatible with the activity of other mitochondrial enzymes involved in DNA replication/repair, e.g. mtSSB, Pol γ, and Lig III, as we were able to reconstitute a multistep reaction of DNA synthesis, flap removal, and nick ligation. Our findings highlight the versatile role of EXOG in maintaining mitochondrial DNA integrity, expanding its DNA processing repertoire to include ssDNA flap removal.

Indexed as

DNA, MitochondrialDNA, Single-StrandedExodeoxyribonucleasesMitochondriaMitochondrial ProteinsBinding SitesDNA-Binding ProteinsDNA RepairDNA ReplicationFlap EndonucleasesHumansDNA-Binding ProteinsDNA, MitochondrialDNA, Single-StrandedExodeoxyribonucleasesFlap EndonucleasesMitochondrial Proteins

Identifiers

PMID40042814
PMCPMC11880807

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Registered trials

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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.