{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310281/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310281"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RPL22L1-dependent translational control of DNA repair confers chemoresistance","description":"Ribosome heterogeneity has emerged as a regulatory layer in gene expression, yet its biological roles in cancers remain poorly understood. Here, we identify RPL22L1, a paralog of the ribosomal protein RPL22, as a key modulator of DNA damage response (DDR) in colorectal cancer cells. DNA damage induces RPL22L1 upregulation and ribosomal incorporation, forming RPL22L1-containing ribosomes. Ribosome profiling revealed that RPL22L1-containing ribosomes preferentially translate mRNAs with highly structured 5’ untranslated region (5’UTR). In particular, RPL22L1 enhances the translation of ATRX through an internal ribosome entry site (IRES)-dependent mechanism. ATRX subsequently recruits DNA-PKcs to DNA damage sites, thereby enhancing the non-homologous end joining (NHEJ) activity. RPL22L1 loss creates exploitable DDR vulnerabilities, sensitizing cancer cells to cisplatin and PARP inhibitors in vitro and in vivo. Collectively, these findings uncover a specialized ribosome-mediated translational program in DDR and highlight RPL22L1 as a potential therapeutic target in DNA damage-based cancer therapy.","dates":{"publication":"2026/06/21"},"accession":"GSE310281","cross_references":{"GSM":["GSM9293331","GSM9293330","GSM9293326","GSM9293328","GSM9293327","GSM9293329"],"GPL":["24676"],"GSE":["310281"],"taxon":["Homo sapiens"]}}