Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination.

The long non-coding telomeric RNA transcript TERRA, in the form of an RNA-DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA-DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.

Effects of intracerebral noradrenaline on cognitive decline associated with the loss of occlusal support.

PURPOSE: The lack of occlusal support reportedly reduces cognitive function; however, the underlying mechanisms remain unclear. The locus coeruleus, which is located adjacent to the trigeminal mesencephalic nucleus, secretes noradrenaline throughout the brain. In this study, we evaluated the effects of noradrenaline in the hippocampus and cerebral cortex on cognitive decline following tooth extraction in rats. METHODS: We performed passive avoidance experiments on male Wistar rats with extracted maxillary molars and determined the neuron density in the locus coeruleus and trigeminal mesencephalic nucleus using immunostaining and Nissl staining, respectively. We also assessed noradrenaline concentrations in the hippocampus and cerebral cortex using enzyme-linked immunosorbent assay. RESULTS: In the passive avoidance experiment, the latency in the bright compartment was significantly shorter (P < 0.05) in the extraction group than in the control group. The numbers of cells in the locus coeruleus and trigeminal nucleus were significantly lower (P < 0.05) in the extraction group compared to those in the control group. The noradrenaline levels in the hippocampus and cerebral cortex were also significantly lower (P < 0.05) in the extraction group than those in the control group. CONCLUSIONS: The lack of occlusal support associated with tooth extraction reduces the number of cells in the trigeminal mesencephalic nucleus and locus coeruleus, which may reduce the supply of noradrenaline to the cerebral cortex and hippocampus, leading to a decline in cognitive function.