TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.This work was supported by funding from the Medical Research Council and the European Research Council (ERC, 281847) (A.P.J.), the Lister Institute for Preventative Medicine (A.P.J. and G.S.S.), Medical Research Scotland (L.S.B.), German Federal Ministry of Education and Research (BMBF, 01GM1404) and E-RARE network EuroMicro (B.W), Wellcome Trust (M. Hurles), CMMC (P.N.), Cancer Research UK (C17183/A13030) (G.S.S. and M.R.H), Swiss National Science Foundation (P2ZHP3_158709) (O.M.), AIRC (12710) and ERC/EU FP7 (CIG_303806) (S.S.), Cancer Research UK (C6/A11224) and ERC/EU FP7 (HEALTH-F2- 2010-259893) (A.N.B. and S.P.J.).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345

Relationship between production of ethylene and a-farnesene in apples, and how it is influenced by the timing of diphenylamine treatment

The relationship between ethylene and peel α-farnesene concentrations was examined by applying diphenylamine (DPA) and the ethylene analogue, propylene at varying times after harvest to superficial scald (scald) susceptible ‘Granny Smith’ apples (Malus domestica Borkh.) stored at 10°C. Delaying DPA application after harvest had no large effect on ethylene or on peel α-farnesene production. Propylene advanced fruit ripening and promoted an increase in peel α-farnesene concentration before endogenous internal ethylene production, suggesting that ethylene has an important regulatory role in α-farnesene production, but their biosynthetic pathways are controlled independently. The effect of delayed DPA application (4 and 7 days after harvest) on the relationship between ethylene and peel α-farnesene was further examined at both a scald-inducing temperature (0°C) and a non-scald-inducing temperature (10°C) with ‘Granny Smith’ and the scald resistant ‘Crofton’ cultivar. Similarly a delayed DPA application had only minor effects on internal ethylene and peel α-farnesene concentrations. The relationship between internal ethylene and peel α-farnesene concentration was dependent on storage temperature, and the type of relationship was independent of cultivar. However, the magnitude of the relationship between cultivars was significantly different (‘Granny Smith’ produced significantly more α-farnesene than ‘Crofton’) and may be related to scald developmen

Fate of apple peel phenolics during cool storage

Consumption of certain phenolics in the diet is considered beneficial to human health. In this study, individual phenolics were measured by diode-array HPLC at monthly intervals in the peel of Granny Smith, Lady Williams, and Crofton apple cultivars stored in air at 0 C for 9 months. The concentrations of total phenolics significantly differed among the cultivars examined, with Lady Williams peel having significantly more phenolics (over 4000 g·g-1 peel fresh weight) than Crofton (2668 g·g-1 peel fresh weight) and Granny Smith, which had the lowest concentration of total phenolics (1275 g·g-1 peel fresh weight). There were also significant differences in individual phenolics among cultivars and during storage. Quercetin glycosides were the only flavonols identified, with quercetin rhamnoglucoside being the most abundant phenolic in the peel. Chlorogenic acid was the major cinnamic acid derivative, with high concentrations, up to 412 g·g-1 peel fresh weight, in Crofton peel. A pre-storage diphenylamine (DPA) treatment had few significant effects on peel phenolic metabolism. Where differences did occur, fruit treated with DPA retained higher concentrations of total peel phenolics during storage than fruit not treated with DPA. Storage of all cultivars for up to 9 months in air at 0 C induced few significant changes in the peel phenolic concentrations. This indicates that phenolic metabolism in apple peel is relatively stable, and the health benefits of phenolics in apple peel should be maintained during long-term storage