Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events.

BACKGROUND: Nucleotide excision repair is the primary DNA repair mechanism that removes bulky DNA adducts such as UV-induced pyrimidine dimers. Correspondingly, genome-wide mapping of nucleotide excision repair with eXcision Repair sequencing (XR-seq), provides comprehensive profiling of DNA damage repair. A number of XR-seq experiments at a variety of conditions for different damage types revealed heterogenous repair in the human genome. Although human repair profiles were extensively studied, how repair maps vary between primates is yet to be investigated. Here, we characterized the genome-wide UV-induced damage repair in gray mouse lemur, Microcebus murinus, in comparison to human. RESULTS: We derived fibroblast cell lines from mouse lemur, exposed them to UV irradiation, and analyzed the repair events genome-wide using the XR-seq protocol. Mouse lemur repair profiles were analyzed in comparison to the equivalent human fibroblast datasets. We found that overall UV sensitivity, repair efficiency, and transcription-coupled repair levels differ between the two primates. Despite this, comparative analysis of human and mouse lemur fibroblasts revealed that genome-wide repair profiles of the homologous regions are highly correlated, and this correlation is stronger for highly expressed genes. With the inclusion of an additional XR-seq sample derived from another human cell line in the analysis, we found that fibroblasts of the two primates repair UV-induced DNA lesions in a more similar pattern than two distinct human cell lines do. CONCLUSION: Our results suggest that mouse lemurs and humans, and possibly primates in general, share a homologous repair mechanism as well as genomic variance distribution, albeit with their variable repair efficiency. This result also emphasizes the deep homologies of individual tissue types across the eukaryotic phylogeny.

Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression.

Protein kinase C (PKC) isozymes are members of the Serine/Threonine kinase family regulating cellular events following activation of membrane bound phospholipids. The breakdown of the downstream signaling pathways of PKC relates to several disease pathogeneses particularly neurodegeneration. PKC isozymes play a critical role in cell death and survival mechanisms, as well as autophagy. Numerous studies have reported that neurodegenerative disease formation is caused by failure of the autophagy mechanism. This review outlines PKC signaling in autophagy and neurodegenerative disease development and introduces some polyphenols as effectors of PKC isozymes for disease therapy.

Magnetofection of Green Fluorescent Protein Encoding DNA-Bearing Polyethyleneimine-Coated Superparamagnetic Iron Oxide Nanoparticles to Human Breast Cancer Cells.

Gene therapy is a developing method for the treatment of various diseases. For this purpose, the search for nonviral methods has recently accelerated to avoid toxic effects. A strong alternative method is magnetofection, which involves the use of superparamagnetic iron oxide nanoparticles (SPIONs) with a proper organic coating and external magnetic field to enhance the localization of SPIONs at the target site. In this study, a new magnetic actuation system consisting of four rare-earth magnets on a rotary table was designed and manufactured to obtain improved magnetofection. As a model, green fluorescent protein DNA-bearing polyethyleneimine-coated SPIONs were used. Magnetofection was tested on MCF7 cells. The system reduced the transfection time (down to 1 h) of the standard polyethyleneimine transfection protocol. As a result, we showed that the system could be effectively used for gene transfer.