Evidence map›Paper›PMID 41513635›Full record

ArticleCell death & disease2026

O-GlcNAcylation of XRCC4 controls its stability and confers resistance to DNA double-strand break damage in cancer cells.

Jeong Yeon Ko, Tae Hyun Kweon, Hyeryeon Jung, Jingu Kang, Yeolhoe Kim, Yun Ju Kim, Donghyuk Shin, Seong Wook Yang, Myeong Min Lee, Jun Young Hong and 4 more

Abstract read
In one paragraph

Article in Cell death & disease, 2026. 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

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.

Jeong Yeon KoDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Tae Hyun KweonDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Hyeryeon JungDepartment of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul, 03080, Republic of Korea.ORCID http://orcid.org/0000-0001-5179-8604
Jingu KangDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Yeolhoe KimDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0003-2832-2493
Yun Ju KimDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Donghyuk ShinDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0002-8272-6133
Seong Wook YangDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Myeong Min LeeDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Jun Young HongDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Jae-Min LimDepartment of Chemistry, College of Natural Sciences, Changwon National University, Changwon, 51140, Republic of Korea.
Eugene C YiDepartment of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul, 03080, Republic of Korea.
Jin Won ChoDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Won Ho YangDepartment of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. bionicwono@yonsei.ac.kr.ORCID http://orcid.org/0000-0001-6214-1421

Funding

National Research Foundation of Korea (NRF) NRF-2018R1A6A1A03025607National Research Foundation of Korea (NRF) NRF-RS-2023-00213643
6 · The paper itself

Abstract

X-ray repair cross-complementing protein 4 (XRCC4), a non-homologous end-joining protein involved in DNA double-strand break repair, is highly expressed in human cancer cells and tissues. A prior OGT interactome study identified XRCC4 as a candidate for O-GlcNAcylation. O-GlcNAcylation levels, a post-translational modification found on nuclear and cytosolic proteins, are also elevated in various cancers. However, the direct regulatory mechanism linking O-GlcNAcylation to XRCC4 function in cancer cells remains unclear. Here, we found that XRCC4 is O-GlcNAcylated at threonine 308, enhancing its stability by inhibiting TRIM21-mediated ubiquitin-dependent proteasomal degradation. O-GlcNAcylation elevated XRCC4 protein levels during DNA double-strand break damage, thereby conferring resistance to such damage. Additionally, XRCC4 Thr308 O-GlcNAcylation promotes cancer proliferation, invasion, and in vivo tumor growth. These findings suggest that downregulating O-GlcNAcylation on XRCC4 could be a potential therapeutic strategy to increase cancer sensitivity to chemotherapy or radiotherapy.

Indexed as

AcetylglucosamineDNA-Binding ProteinsDNA Breaks, Double-StrandedNeoplasmsAnimalsCell Line, TumorCell ProliferationDNA RepairHumansMiceMice, NudeProtein Processing, Post-TranslationalProtein StabilityAcetylglucosamineDNA-Binding ProteinsXRCC4 protein, human

Identifiers

PMID41513635
PMCPMC12789502

What Socratic holds

Textmetadata
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 Socratic graph.