2026-07-25T03:54:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/275952026-07-17T00:15:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Ayra-Plasencia, Jessel
author
Jorge, Inmaculada
author
Vázquez, Jesús
author
Freire, Raimundo
author
Smits, Veronique A J
2026-07-16T09:53:36Z
2026-07-16T09:53:36Z
2026-04-16
Cell Rep. 2026 Apr 16;45(4):117279.
CELL REPORTS
41996237
https://hdl.handle.net/20.500.12105/27595
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.
eng
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.
research article
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URL
https://repisalud.isciii.es/bitstreams/1347e8f5-7b1b-4b0d-8666-7177c8d19d13/download
File
MD5
d89dd26644a2f037c2045201b6eb4b51
13568438
application/pdf
RNF126 and BRAP safeguard_Cell Rep_2026.pdf