SAW1 is required for efficient removal by the Rad1-Rad10 nuclease of 3′ non-homologous DNA ends (flaps) formed as intermediates during two modes of double-strand break repair in S. cerevisiae, single-strand annealing (SSA) and synthesis-dependent strand annealing (SDSA). Saw1 was shown in vitro to bind flaps with high affinity, but displayed diminished affinity when flaps were short (< 30 deoxynucleotides [nt]), consistent with it not being required for short flap cleavage. Accordingly, this study, using in vivo fluorescence microscopy showed that SAW1 was not required for recruitment of Rad10-YFP to DNA double-strand breaks (DSBs) during their repair by SSA when the flaps were ~10 nt. In contrast, recruitment of Rad10-YFP to DSBs when flaps were ~500 nt did require SAW1 in G1 phase of cell cycle. Interestingly, we observed a substantial increase in colocalization of Saw1-CFP and Rad10-YFP at DSBs when short flaps were formed during repair, especially in G1, indicating significant recruitment of Saw1 despite there being no requirement for Saw1 to recruit Rad10. Saw1-CFP was seldom observed at DSBs without Rad10-YFP. Together these results support a model in which Saw1, and Rad1-Rad10 are recruited as a complex to short and long flaps in all phases of cell cycle, but that Saw1 is only required for recruitment of Rad1-Rad10 to DSBs when long flaps are formed in G1.

This case report describes long-term therapeutic management in a 33-year-old diagnosed with Candida vulvovaginitis and vulvar hidradenitis suppurativa 47 months previously. Candida spp. yeasts are part of many women's normal vaginal microflora, and the development of vulvovaginal candidiasis is typically a result of a disturbance in the patient's microbial ecosystem, which manifests itself by intense pruritus, erythema, swelling, and thick white vaginal discharge. Hidradenitis suppurativa is a chronic auto-inflammatory skin condition that causes painful weeping lesions in areas of dense apocrine glands. Although certain mechanisms underlying the pathogenesis of Hidradenitis Suppurativa (e.g., risk factors include smoking, obesity, and family history) have been investigated, a definitive explanation remains elusive. Nutritional intervention in the form of an all-meat ketogenic diet may be considered therapy in the management of both diseases, as successfully seen in this case report. The patient refused standard of care with oral fluconazole for Candida vulvovaginitis and surgical removal for Hidradenitis suppurativa, and instead consumed a zero-carbohydrate all-meat ketogenic diet mostly of beef with strict adherence to the diet for 43 days in which symptoms ceased.

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