2026-07-25T03:54:44Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/275952026-07-17T00:15:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Ayra-Plasencia, Jessel author Jorge, Inmaculada author Vázquez, Jesús author Freire, Raimundo author Smits, Veronique A J author 2026-04-16 DNA double-strand breaks generated during mitosis are thought to be inefficiently repaired, yet cellular responses to damage incurred specifically in late mitosis remain poorly understood. Here, we report that irradiation of cells synchronized in anaphase/telophase triggers partial DNA damage signaling, marked by H2AX phosphorylation and MDC1 accumulation. Consequently, cells enter G1 and S phases with unrepaired lesions. Proteomic analysis identified the E3 ubiquitin ligases RNF126 and BRAP as key regulators of this response, based on their selective ATM-dependent accumulation in irradiated late mitotic cells. Functional assays reveal that both proteins are required for damage-induced 53BP1 and RPA2 focus formation, resolution of DNA lesions, and survival after damage in late mitosis. Supporting their clinical relevance, both E3 ligases are overexpressed in selected tumors and associated with chromosomal instability. These findings suggest that RNF126 and BRAP help cells tolerate late mitotic damage and may represent potential vulnerabilities for improving genotoxic therapies in cancer. Cell Rep. 2026 Apr 16;45(4):117279. CELL REPORTS 41996237 https://hdl.handle.net/20.500.12105/27595 BRAP CP: genomics DNA damage response RNF126 cell cycle checkpoint chromosomal instability double-strand break ionizing radiation late mitosis replication stress ubiquitin ligase RNF126 and BRAP safeguard genome integrity after DNA damage in late mitosis.