Evidence map›Paper›PMID 41285797›Full record

ArticleNature communications2025

53BP1-RIF1 and DNA-PKcs show distinct genetic interactions with diverse chromosomal break repair outcomes.

Kaela Makins, Metztli Cisneros-Aguirre, Felicia Wednesday Lopezcolorado, Jeremy M Stark

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Kaela MakinsDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0009-0002-9934-0832
Metztli Cisneros-AguirreDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Felicia Wednesday LopezcoloradoDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Jeremy M StarkDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA, USA. jstark@coh.org.ORCID http://orcid.org/0000-0002-2625-5373

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3M
Elucidating the role of DNAPKcs in chromosomal break end joining and clastogen resistanceR01CA256989 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI STARK, JEREMY MICHAEL · 2021 to 2025
$2.1M
Defining the role of chromosomal break end synapsis factors for DNA repairF99CA284248 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CISNEROS, METZTLI · 2023 to 2023
$33k
NCI NIH HHS F99 CA284248NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA256989U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) F99CA284248U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA33572
6 · The paper itself

Abstract

53BP1 accumulates at DNA double strand breaks (DSBs) and is implicated in non-homologous end joining (NHEJ), but the genetic interplay of 53BP1 with the NHEJ pathway (e.g., DNA-PKcs) is poorly understood. We examine blunt DSB NHEJ of Cas9 DSBs, which is dependent on core NHEJ factors, and find that loss of 53BP1 does not affect such repair but causes a reduction when combined with DNA-PKcs disruption. In contrast, disrupting 53BP1 and DNA-PKcs, alone and together, has similar effects on the type of deletion mutation (increase in microhomology deletions). We find similar effects with RIF1, such that 53BP1-RIF1 appear to play a backup role for DNA-PKcs during blunt DSB NHEJ, but function in the same pathway to suppress microhomology deletions. Finally, DNA-PKcs kinase inhibition causes increased radiosensitivity and homology-directed repair that is not additive with loss of 53BP1. Altogether, 53BP1-RIF1 and DNA-PKcs show distinct genetic interactions with diverse DSB repair outcomes.

Indexed as

DNA-Activated Protein KinaseDNA End-Joining RepairTelomere-Binding ProteinsTumor Suppressor p53-Binding Protein 1AnimalsDNA Breaks, Double-StrandedDNA RepairHumansMiceRadiation ToleranceDNA-Activated Protein KinaseRif1 protein, mouseTelomere-Binding ProteinsTP53BP1 protein, humanTrp53bp1 protein, mouseTumor Suppressor p53-Binding Protein 1

Identifiers

PMID41285797
PMCPMC12644711

What Socratic holds

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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.