Evidence map›Paper›PMID 39893637›Full record

ArticleCell reports2025

The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability.

Emily Graham, Lucia Rampazzo, Chin Wei Brian Leung, Jacob Wall, Emőke Zsanett Gerőcz, Mikhail Liskovykh, Nikolay Goncharov, Xanita Saayman, Ramazan Gundogdu, Masato T Kanemaki and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. 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
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.

  1. Article
  2. Article
  3. Article
  4. 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

14 authors.

Emily GrahamSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Lucia RampazzoSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Chin Wei Brian LeungSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Jacob WallSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Emőke Zsanett GerőczSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Mikhail LiskovykhDevelopmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nikolay GoncharovDevelopmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Xanita SaaymanSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Ramazan GundogduSir William Dunn School of Pathology, University of Oxford, Oxford, UK; Department of Pharmacy Services, Vocational School of Health Services, Bingol University, Bingol, Türkiye.
Masato T KanemakiDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Shizuoka, Japan; Department of Advanced Studies, SOKENDAI, Shizuoka, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Hiroshi MasumotoLaboratory of Chromosome Engineering, Department of Frontier Research and Development, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818d, Japan.
Vladimir LarionovDevelopmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Natalay KouprinaDevelopmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fumiko EsashiSir William Dunn School of Pathology, University of Oxford, Oxford, UK. Electronic address: fumiko.esashi@path.ox.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/Y512928/1Medical Research Council MR/W017601
6 · The paper itself

Abstract

Centromeres are crucial for chromosome segregation but are vulnerable to breakage and recombination due to their repetitive DNA. The mechanisms protecting centromeres from these instabilities remain incompletely understood. This study investigates the role of the homologous recombination (HR) mediators BRCA2 and PALB2 in centromere stability. We find that BRCA2, but not PALB2, is essential for maintaining a human artificial chromosome. In native chromosomes, BRCA2 ensures CENP-A occupancy and prevents DNA fragility at centromeres. Conversely, PALB2 does not affect CENP-A, whereas its depletion increases centromeric DNA breaks in non-cancerous cells only. Interestingly, depleting the mismatch repair (MMR) factor MLH1 masks centromere fragility caused by BRCA2 or PALB2 loss, suggesting that MLH1 contributes to DNA instability when BRCA2 or PALB2 is absent. However, cells deficient in both BRCA2/PALB2 and MLH1 have reduced survival. These results highlight a critical balance between HR and MMR factors in preserving centromere integrity and cell viability.

Indexed as

BRCA2 ProteinCentromereDNA Mismatch RepairFanconi Anemia Complementation Group N ProteinHomologous RecombinationCell SurvivalCentromere Protein AHumansMutL Protein Homolog 1BRCA2 ProteinBRCA2 protein, humanCentromere Protein AFanconi Anemia Complementation Group N ProteinMLH1 protein, humanMutL Protein Homolog 1PALB2 protein, humanBRCA2CENP-AcentromereschromosomesCP: Molecular biologyexo-FISHHACHRMLH1MMRPALB2

Identifiers

PMID39893637
PMCPMC11860765

What Socratic holds

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LicenceCC BY
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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 Socratic graph.