Evidence map›Paper›PMID 38533616›Full record

ArticleMolecular oncology2024

The one-carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation.

Petra Marttila, Nadilly Bonagas, Christina Chalkiadaki, Hannah Stigsdotter, Korbinian Schelzig, Jianyu Shen, Crystal M Farhat, Amber Hondema, Julian Albers, Elisée Wiita and 5 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact, top 96% 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

4 citing papers in PubMed, 0 citations in OpenAlex.

  1. MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026
    Review
  2. Review
  3. Review
  4. MTHFD2: A Retrospective and a Glance into the Future.International journal of molecular sciences · 2025
    Review
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

15 authors at 1 institution in 2 countries.

Petra MarttilaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.ORCID 0000-0002-0115-8067
Nadilly BonagasScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Christina ChalkiadakiScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Hannah StigsdotterScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Korbinian SchelzigScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.ORCID 0009-0001-3791-0716
Jianyu ShenScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Crystal M FarhatScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Amber HondemaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Julian AlbersScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Elisée WiitaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Azita RastiScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Ulrika Warpman BerglundScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Ana SlipicevicScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Oliver MortusewiczScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.ORCID 0000-0002-4290-4994
Thomas HelledayScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.ORCID 0000-0002-7384-092X
Science for Life Laboratory · SE

Funding

Karolinska Institute's KID-funding for Doctoral StudentsSwedish Cancer Society 21-1490Swedish Childhood Cancer Fund 2021-0030The Erasmus+ programme of the European UnionThe Helleday FoundationThe Swedish Cancer Society Radiation Biology Programme 22-2108The Swedish Innovation Agency 2021-04817The Swedish Research Council 2015-00162
6 · The paper itself

Abstract

The one-carbon metabolism enzyme bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is among the most overexpressed proteins across tumors and is widely recognized as a promising anticancer target. While MTHFD2 is mainly described as a mitochondrial protein, a new nuclear function is emerging. Here, we observe that nuclear MTHFD2 protein levels and association with chromatin increase following ionizing radiation (IR) in an ataxia telangiectasia mutated (ATM)- and DNA-dependent protein kinase (DNA-PK)-dependent manner. Furthermore, repair of IR-induced DNA double-strand breaks (DSBs) is delayed upon MTHFD2 knockdown, suggesting a role for MTHFD2 in DSB repair. In support of this, we observe impaired recruitment of replication protein A (RPA), reduced resection, decreased IR-induced DNA repair protein RAD51 homolog 1 (RAD51) levels and impaired homologous recombination (HR) activity in MTHFD2-depleted cells following IR. In conclusion, we identify a key role for MTHFD2 in HR repair and describe an interdependency between MTHFD2 and HR proficiency that could potentially be exploited for cancer therapy.

Indexed as

AminohydrolasesHomologous RecombinationMethylenetetrahydrofolate Dehydrogenase (NADP)Multifunctional EnzymesRadiation, IonizingCarbonCell Line, TumorDNA Breaks, Double-StrandedDNA RepairHumansAminohydrolasesCarbonMethylenetetrahydrofolate Dehydrogenase (NADP)MTHFD2 protein, humanMultifunctional EnzymesDSB repairhomologous recombinationionizing radiationMTHFD2

Identifiers

PMID38533616
PMCPMC11467796
OpenAlexW4393227242

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.