Evidence map›Paper›PMID 39631396›Full record

ArticleMolecular cell2025

Two-ended recombination at a Flp-nickase-broken replication fork.

Rajula Elango, Namrata M Nilavar, Andrew G Li, Daniel Nguyen, Emilie Rass, Erin E Duffey, Yuning Jiang, Abdulkadir Abakir, Nicholas A Willis, Jonathan Houseley and 1 more

Abstract read
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Review
  2. Article
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  9. Review
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  11. Asymmetrical recognition and processing of double-strand breaks formed during DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Review
  13. Review
  14. Mechanisms and genomic implications of break-induced replication.Nature structural & molecular biology · 2025
    Review
  15. Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025
    Review
  16. Research square · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Rajula ElangoDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Namrata M NilavarDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Andrew G LiDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Daniel NguyenDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Emilie RassDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Erin E DuffeyDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Yuning JiangDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Abdulkadir AbakirThe Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Nicholas A WillisDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Jonathan HouseleyThe Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Ralph ScullyDepartment of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: rscully@bidmc.harvard.edu.

Funding

Stalled replication fork repair in cancer predisposition and cancertherapyR35CA263813 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Ralph Scully · 2022 to 2026
$5.1M
NCI NIH HHS R35 CA263813Wellcome Trust
6 · The paper itself

Abstract

Replication fork collision with a DNA nick can generate a one-ended break, fostering genomic instability. The opposing fork's collision with the nick could form a second DNA end, enabling conservative repair by homologous recombination (HR). To study mechanisms of nickase-induced HR, we developed the Flp recombinase "step arrest" nickase in mammalian cells. A Flp-nick induces two-ended, BRCA2/RAD51-dependent short tract gene conversion (STGC), BRCA2/RAD51-independent long tract gene conversion, and discoordinated two-ended invasions. HR pathways induced by a replication-independent break and the Flp-nickase differ in their dependence on BRCA1, MRE11, and CtIP. To determine the origin of the second DNA end during Flp-nickase-induced STGC, we blocked the opposing fork using a Tus/Ter replication fork barrier (RFB). Flp-nickase-induced STGC remained robust and two ended. Thus, a single replication fork's collision with a Flp-nick triggers two-ended HR, possibly reflecting replicative bypass of lagging strand nicks. This response may limit genomic instability during replication of nicked DNA.

Indexed as

BRCA2 ProteinDNA-Binding ProteinsDNA NucleotidyltransferasesDNA ReplicationRad51 RecombinaseBRCA1 ProteinCarrier ProteinsDeoxyribonuclease IEndodeoxyribonucleasesGene ConversionGenomic InstabilityHomologous RecombinationHumansMRE11 Homologue ProteinNuclear ProteinsBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanCarrier ProteinsDeoxyribonuclease IDNA-Binding ProteinsDNA NucleotidyltransferasesEndodeoxyribonucleasesFLP recombinaseMRE11 Homologue ProteinMRE11 protein, humanNuclear ProteinsRAD51 protein, humanRad51 RecombinaseRBBP8 protein, humanBRCA1break-induced replicationCamptothecinDNA nickDNA-protein crosslinkFlp recombinasehomologous recombinationreplication fork breakagereplication stressTus/Ter

Identifiers

PMID39631396
PMCPMC11733529

What OpenQuestion holds

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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.