Programs supporting incarcerated and previously incarcerated indigenous peoples: a scoping review protocol.

The overincarceration of Indigenous peoples and its impacts on individual and community health is a growing concern across Canada and the United States. Federally run Healing Lodges in Canada are an example of support services for incarcerated and previously incarcerated Indigenous peoples to reintegrate into community and support their healing journey. However, there is a need to synthesise research which investigates these programmes. We report a protocol for a scoping review that is guided by the following research question: What is known about culturally informed programmes and services available to incarcerated and previously incarcerated Indigenous peoples in Canada and the US? This scoping review will follow guidelines published by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. This review will only identify programmes that are guided by Indigenous ways of being and knowing in order to best serve Indigenous communities and our community partners. The results of this review will support the development of programmes that are necessary for understanding and addressing the diverse needs of incarcerated and previously incarcerated Indigenous peoples.

FAN1 exo- not endo-nuclease pausing on disease-associated slipped-DNA repeats: A mechanism of repeat instability.

Ongoing inchworm-like CAG and CGG repeat expansions in brains, arising by aberrant processing of slipped DNAs, may drive Huntington's disease, fragile X syndrome, and autism. FAN1 nuclease modifies hyper-expansion rates by unknown means. We show that FAN1, through iterative cycles, binds, dimerizes, and cleaves slipped DNAs, yielding striking exo-nuclease pauses along slip-outs: 5'-C↓A↓GC↓A↓G-3' and 5'-C↓T↓G↓C↓T↓G-3'. CAG excision is slower than CTG and requires intra-strand A·A and T·T mismatches. Fully paired hairpins arrested excision, whereas disease-delaying CAA interruptions further slowed excision. Endo-nucleolytic cleavage is insensitive to slip-outs. Rare FAN1 variants are found in individuals with autism with CGG/CCG expansions, and CGG/CCG slip-outs show exo-nuclease pauses. The slip-out-specific ligand, naphthyridine-azaquinolone, which induces contractions of expanded repeats in vivo, requires FAN1 for its effect, and protects slip-outs from FAN1 exo-, but not endo-, nucleolytic digestion. FAN1's inchworm pausing of slip-out excision rates is well suited to modify inchworm expansion rates, which modify disease onset and progression.