53BP1 Repair Kinetics for Prediction of In Vivo Radiation Susceptibility in 15 Mouse Strains.

We present a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe). Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 mice strains. We previously reported strong evidence for clustering of nearby DSB into single repair units as opposed to the classic "contact-first" model where DSB are considered immobile.

Regulation of photoprotection gene expression in by a putative E3 ubiquitin ligase complex and a homolog of CONSTANS.

Photosynthetic organisms use nonphotochemical quenching (NPQ) mechanisms to dissipate excess absorbed light energy and protect themselves from photooxidation. In the model green alga , the capacity for rapidly reversible NPQ (qE) is induced by high light, blue light, and UV light via increased expression of and genes that are necessary for qE. Here, we used a forward genetics approach to identify SPA1 and CUL4, components of a putative green algal E3 ubiquitin ligase complex, as critical factors in a signaling pathway that controls light-regulated expression of the and genes in The and mutants accumulate increased levels of LHCSR1 and PSBS proteins in high light, and unlike the wild type, they express LHCSR1 and exhibit qE capacity even when grown in low light.

Dose, LET and Strain Dependence of Radiation-Induced 53BP1 Foci in 15 Mouse Strains Introducing Novel DNA Damage Metrics.

We present a comprehensive comparative analysis on the repair of radiation-induced DNA damage in 15 strains of mice, including 5 inbred reference strains and 10 collaborative-cross strains, of both sexes, totaling 5 million skin fibroblast cells imaged by three-dimensional highthroughput conventional microscopy. Non-immortalized primary skin fibroblasts derived from 76 mice were subjected to increasing doses of both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe), which are relevant to carcinogenesis and human space exploration. Automated image quantification of 53BP1 radiation-induced foci (RIF) formation and repair during the first 4-48 h postirradiation was performed as a function of dose and LET.