ABSTRACT Non-homologous end joining (NHEJ), as one major pathway of DNA double-strand break (DSB) repair, could cause genomic instability, which plays pivotal roles in cancer development.

While, chromatin remodeling complexes dictate the selection and orchestration of DSB repair pathways by regulating chromatin dynamics. However, the crosstalk between NHEJ and chromatin

remodeling in cancer progress remains unclear. In this study, deficiency of GLTSCR1 causes resistance to DNA damage in colorectal cancer (CRC) cells by promoting NHEJ repair efficiency.

Mechanistically, GLTSCR1 interacts with BRD9 to engage in the assembly of the non-canonical BAF complex (GBAF). However, GLTSCR1 deficiency disrupts GBAF and triggers the ubiquitination

confirm GLTSCR1 deficiency as a critical regulatory event of the NHEJ pathway in CRC development, which might require different therapeutic strategy for GLTSCR1 wild-type and mutant CRC.

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support SIMILAR CONTENT BEING VIEWED BY OTHERS CRL4ADTL DEGRADES DNA-PKCS TO MODULATE NHEJ REPAIR AND INDUCE GENOMIC INSTABILITY AND SUBSEQUENT MALIGNANT TRANSFORMATION Article Open access

24 February 2021 SMYD3 PROMOTES ENDOMETRIAL CANCER THROUGH EPIGENETIC REGULATION OF LIG4/XRCC4/XLF COMPLEX IN NON-HOMOLOGOUS END JOINING REPAIR Article Open access 08 January 2024 RHNO1: AT

THE CROSSROADS OF DNA REPLICATION STRESS, DNA REPAIR, AND CANCER Article 06 August 2024 DATA AVAILABILITY The data generated in this study are available within the article and its

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formation and regulates homologous recombination-mediated repair. Nat Commun. 2020;11:2639. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We

thank Qiong Huang from the core facility platform of Zhejiang University School of Medicine for technical support. We thank the Laboratory Animal Center of Zhejiang University for technical

assistance with management of mice. FUNDING This work was supported by National Natural Science Foundation of China (grants 81871937, 82472952 and 82173223), the CAMS Innovation Fund for

Medical Sciences (CIFMS, grant number 2019-I2M-5-044) and the Guangdong Basic and Applied Basic Research Foundation (grant number 2023A1515140182). AUTHOR INFORMATION Author notes * These

authors contributed equally: Fengyan Han, Xiaoxu Zhou. AUTHORS AND AFFILIATIONS * Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital (Yiwu),

Zhejiang University School of Medicine, Hangzhou, 310058, China Fengyan Han, Lu Liu, Enping Xu & Honghe Zhang * School of Basic Medical Science, The Fourth Affiliated Hospital, Guangzhou

Medical University, Guangzhou, 511436, China Fengyan Han * Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s Hospital and Institute of Translational Medicine,

Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China Xiaoxu Zhou * Department of Pathology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang,

310006, China Beibei Yang * Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China Pengyuan Liu *

Department of Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, 322000, China Zhe Tang * Department of Surgery, The

Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China Zhe Tang Authors * Fengyan Han View author publications You can also search for this author

inPubMed Google Scholar * Xiaoxu Zhou View author publications You can also search for this author inPubMed Google Scholar * Lu Liu View author publications You can also search for this

author inPubMed Google Scholar * Beibei Yang View author publications You can also search for this author inPubMed Google Scholar * Pengyuan Liu View author publications You can also search

for this author inPubMed Google Scholar * Enping Xu View author publications You can also search for this author inPubMed Google Scholar * Zhe Tang View author publications You can also

search for this author inPubMed Google Scholar * Honghe Zhang View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Conceptualization, HZ, FH, EX

and ZT; methodology, FH, XZ, and LL; investigation, BY, PL and LL; writing—original draft, FH, XZ; writing—review & editing, HZ, FH, EX and ZT; funding acquisition, HZ and FH;

resources, HZ and FH; Supervision, HZ and FH and all authors have approved the final version of the manuscript. CORRESPONDING AUTHORS Correspondence to Fengyan Han, Enping Xu, Zhe Tang or

Honghe Zhang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ETHICS APPROVAL AND CONSENT TO PARTICIPATE All methods in this study were performed in

accordance with the Declaration of Helsinki and its subsequent revisions. Colorectal carcinoma samples from patients in this study were collected from the Run Run Shaw Hospital, Zhejiang

University. All participating patients were informed. The study was approved by the Ethic Committee of Zhejiang University, school of Medicine (Approval number: 2018‐018) and informed

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colorectal cancer development through regulating non-homologous end joining. _Oncogene_ 43, 3517–3531 (2024). https://doi.org/10.1038/s41388-024-03179-x Download citation * Received: 23 May

2024 * Revised: 18 September 2024 * Accepted: 23 September 2024 * Published: 11 October 2024 * Issue Date: 22 November 2024 * DOI: https://doi.org/10.1038/s41388-024-03179-x SHARE THIS

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