Evidence map›Paper›PMID 41489901›Full record

ArticleThe Journal of biological chemistry2025

DNA-damage dependent isoform switching modulates RIF1 DNA repair complex assembly and phase separation.

Adenine Si-Hui Koo, Weiyan Jia, Sang Hwa Kim, Mark Scalf, Claire E Boos, Yuhong Chen, Demin Wang, Andrew F Voter, Aditya Bajaj, Lloyd M Smith and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 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. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Adenine Si-Hui KooDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Weiyan JiaDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sang Hwa KimDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Mark ScalfDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Claire E BoosDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Yuhong ChenVersiti Blood Research Institute, Milwaukee, Wisconsin, USA.
Demin WangVersiti Blood Research Institute, Milwaukee, Wisconsin, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Andrew F VoterDepartment of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Aditya BajajDepartment of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Lloyd M SmithDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
James L KeckDepartment of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Christopher J BakkenistDepartment of Radiation Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Lin GuoDepartment of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Randal S TibbettsDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address: rstibbetts@wisc.edu.

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Justine Yang Bruce · 1985 to 2026
$142.6M
Revealing Proteoforms: The Primary Effectors of Biological FunctionR35GM126914 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Lloyd M Smith · 2018 to 2026
$6.2M
B cell responses in heparin-induced thrombocytopeniaR01HL130724 · NHLBI · VERSITI WISCONSIN, INC. · PI WANG, DEMIN · 2017 to 2024
$4.8M
PLC?s in B cell biology and autoimmunityR01AI079087 · NIAID · VERSITI WISCONSIN, INC. · PI WANG, DEMIN · 2008 to 2018
$4.4M
The Impact of ATR Kinase Inhibitors on CD8+ T Cell Expansion and Memory DevelopmentR01CA266172 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2022 to 2026
$2.3M
DNA damage signaling to dormant origins of replicationR01CA236367 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAKKENIST, CHRISTOPHER J. · 2020 to 2024
$1.8M
Genetic analysis of UBQLN2-associated neurodegeneration in frontotemporal dementiaRF1AG069483 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI TIBBETTS, RANDAL SCOT · 2020 to 2020
$1.7M
Genome maintenance functions of CREB/ATF transcription factorsR01CA180765 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI TIBBETTS, RANDAL SCOT · 2013 to 2016
$1.1M
A Point-Scanning Confocal Microscope for the Biomedical SciencesS10OD034394 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI MERRINS, MATTHEW J. · 2023 to 2023
$537k
Genetic enhancement of CREB signaling in Rett SyndromeR21NS118792 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI TIBBETTS, RANDAL SCOT · 2020 to 2021
$427k
NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA180765NCI NIH HHS R01 CA236367NCI NIH HHS R01 CA266172NHLBI NIH HHS R01 HL130724NIAID NIH HHS R01 AI079087NIA NIH HHS RF1 AG069483NIGMS NIH HHS R35 GM126914NIH HHS S10 OD034394NINDS NIH HHS R21 NS118792
6 · The paper itself

Abstract

How RIF1 (RAP1 interacting factor 1) fulfills its diverse roles in DNA double-strand break repair, DNA replication, and nuclear organization remains elusive. Here, we show that alternative splicing of a cassette exon (Ex32) encoding a Ser/Lys-rich cassette in the RIF1 C-terminal domain (CTD) gives rise to RIF1-Long (RIF1-L) and RIF1-Short (RIF1-S) isoforms with different functional characteristics. We demonstrate that RIF1-Ex32 splice-in is mediated by an exonic splicing enhancer that is recognized by the serine and arginine rich splicing factor 1 (SRSF1) and antagonized by SRSF3 and SRSF7. Exposure to DNA damage inhibited Ex32 splice-in, potentiated the association of SRSF3 and SRSF7 with RIF1 pre-mRNA, and caused an increase in RIF1-S protein expression, which was also observed across a diverse set of primary cancers. Isoform-specific proteomic analyses revealed RIF1-L preferentially associated with mediator of DNA damage checkpoint 1 (MDC1) and sustained MDC1 focus formation to a greater extent than RIF1-S. We further show that the Ser/Lys-rich cassette stabilized a novel phase separation activity of the RIF1 CTD and enhanced RIF1-L chromatin retention, which was reversed by cyclin-dependent kinase 1-dependent phosphorylation of the RIF1 CTD in response to G

Indexed as

Alternative SplicingDNA DamageDNA RepairTelomere-Binding ProteinsAdaptor Proteins, Signal TransducingCDC2 Protein KinaseCell Cycle ProteinsExonsHumansPhase SeparationProtein IsoformsSerine-Arginine Splicing FactorsAdaptor Proteins, Signal TransducingCDC2 Protein KinaseCDK1 protein, humanCell Cycle ProteinsMDC1 protein, humanProtein IsoformsRif1 protein, humanSerine-Arginine Splicing FactorsSRSF1 protein, humanTelomere-Binding Proteinsalternative splicingcell signalingchromatinDNA damageMDC1RIF1RNA binding protein

Identifiers

PMID41489901
PMCPMC12702018

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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.