ARID1B promotes DNA end resection via MDC1 and co-transactivation of DNA repair genes with c-MYC in small cell lung cancerDownload PDF Download PDF ArticleOpen accessPublished: 12 October 2026Peng Hou1,2,3,Gongfeng Li ORCID: orcid.org/0009-0006-8488-10531,2,3,Guozhen Cao2,3,Xinhuang Yao3,Honglin Li4,Jiahui Zhang ORCID: orcid.org/0000-0002-2013-02893,Jinghan Hua1,2,Rui Guo3,Li Xiang ORCID: orcid.org/0000-0002-7164-05883 &…Wenchu Lin ORCID: orcid.org/0000-0001-6141-17253 Cell Death & Disease (2026) Cite this articleSave articleView saved research We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.AbstractAT-rich interactive domain-containing protein 1B (ARID1B) has been implicated in DNA damage repair; however, its precise molecular mechanisms and contributions to small cell lung cancer (SCLC) pathogenesis remain incompletely defined. In this study, analysis of clinical datasets revealed that ARID1B is significantly overexpressed in SCLC tissues and cell lines compared to normal lung tissues or lung adenocarcinoma counterparts. Functional studies in vitro and in vivo demonstrated that ARID1B depletion markedly impairs SCLC cell proliferation, clonogenicity, and tumor growth while accelerating apoptosis. Mechanistically, during the DNA double-strand break (DSB) response, ARID1B cooperates with the transcription factor c-MYC to co-activate the transcription of key DNA damage repair (DDR) genes, such as RNF8 and RAD51. Concurrently, ARID1B is rapidly recruited to DSB sites, where it facilitates single-stranded DNA (ssDNA) formation via end resection and promotes the recruitment of MDC1, a scaffold protein essential for early DDR signaling. Critically, ARID1B deficiency profoundly sensitizes SCLC cells to DNA-damaging agents, as evidenced by enhanced DNA damage persistence, apoptosis, and tumor growth inhibition in vitro and in vivo. Taken together, this study unveils a dual regulatory role of ARID1B in homologous recombination (HR) repair and establishes its potential as a therapeutic target to potentiate the efficacy of frontline chemotherapy in SCLC.AcknowledgementsWe thank members of the Lin laboratory for critical reading of the manuscript and helpful discussions.FundingThis study was supported by National Natural Science Foundation of China (Grant Numbers: 82573883 to WL and 82303091 to GC), Shenzhen Science and Technology Program (Grant Number: JCYJ20250604180129038), Key Medical Technologies R & D Programme of Longang district (Grant Number: LGKCYLWS2023012), A portion of this work was supported by Sanming Project of Medicine in Shenzhen.Author informationAuthors and AffiliationsHigh Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, P.R. ChinaPeng Hou, Gongfeng Li & Jinghan HuaUniversity of Science and Technology of China, Hefei, P.R. ChinaPeng Hou, Gongfeng Li, Guozhen Cao & Jinghan HuaThe Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, P.R. ChinaPeng Hou, Gongfeng Li, Guozhen Cao, Xinhuang Yao, Jiahui Zhang, Rui Guo, Li Xiang & Wenchu LinShenzhen University Medical School, Shenzhen, P.R. ChinaHonglin LiAuthorsPeng HouView author publicationsSearch author on:PubMed Google ScholarGongfeng LiView author publicationsSearch author on:PubMed Google ScholarGuozhen CaoView author publicationsSearch author on:PubMed Google ScholarXinhuang YaoView author publicationsSearch author on:PubMed Google ScholarHonglin LiView author publicationsSearch author on:PubMed Google ScholarJiahui ZhangView author publicationsSearch author on:PubMed Google ScholarJinghan HuaView author publicationsSearch author on:PubMed Google ScholarRui GuoView author publicationsSearch author on:PubMed Google ScholarLi XiangView author publicationsSearch author on:PubMed Google ScholarWenchu LinView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Wenchu Lin.Ethics declarationsCompeting interestsThe authors declare no competing interests.Ethical approvalAll mouse experiments were performed in compliance with the institutional guidelines and the protocol was approved by the Ethics Committee of Longgang District People’s Hospital of Shenzhen(2024067DW) (2026087ANM).Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Edited by Professor Giorgio StassiSupplementary informationRights and permissionsOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Reprints and permissionsAbout this article