Soeda, S. | Search bioRxiv

bioRxiv2026

Age-dependent accumulation of RAD51 on non-damaged chromosomes prevents chromosome segregation in mammalian oocytes

RAD51 is targeted to single-stranded (ss)DNA for homologous recombination and DNA replication fork homeostasis. However, the physiological consequences of RAD51 binding to intact double-stranded (ds)DNA, which is tightly limited in vivo, remain elusive. Here we revealed an intrinsic property of RAD51 to bind chromosome axes where cohesin and condensin bind, which is actively suppressed by FIGNL1 AAA+ ATPase. In Fignl1-deficient mouse oocytes, an age-dependent RAD51 accumulation with little DNA damage leads to improper chromosomal localization of condensin II and topoisomerase II, failure in chromosome condensation with massive chromosome entanglement, and meiosis I arrest. We propose that promiscuous RAD51 binding to non-damaged chromosomes, which is prevented by a RAD51 remodeler, is a unique type of chromosomal pathology associated with genome instability.

cell biology↗

bioRxiv2020

Aberrant claudin-6-adhesion signal promotes endometrial cancer progression via estrogen receptor α

Cell adhesion proteins not only maintain tissue integrity but also possess signaling abilities to organize diverse cellular events in physiological and pathological processes; however, the underlying mechanism remains obscure. Among cell adhesion molecules, the claudin (CLDN) family often possesses aberrant expression in various cancers, but the biological relevance and molecular basis have not yet been established. Here, we show that high CLDN6 expression promotes endometrial cancer progression and represents the poor prognostic marker. The second extracellular domain and Y196/200 of CLDN6 were required to recruit and activate Src-family kinases (SFKs) and to stimulate malignant phenotypes. Importantly, we demonstrate that the CLDN6/SFK/PI3K-dependent AKT and SGK (serum- and glucocorticoid-regulated kinase) signalings target Ser518 in the human estrogen receptor and ligand-independently activate target genes in endometrial cancer cells, resulting in cancer development. The identification of this machinery highlights regulation of the transcription factors by cell adhesion to advance tumor progression.

cancer biology↗