Scopul nostru este sprijinirea şi promovarea cercetării ştiinţifice şi facilitarea comunicării între cercetătorii români din întreaga lume.
Cells are under constant attack from genotoxins and rely on a multifaceted DNA damage response (DDR) network to maintain genomic integrity. Central to the DDR are the ATM and ATR kinases, which respond primarily to double-strand DNA breaks (DSBs) and replication stress, respectively. Optimal ATR signaling requires the RAD9A-RAD1-HUS1 (9-1-1) complex, a toroidal clamp that is loaded at damage sites and scaffolds signaling and repair factors. WhereasRead more
We describe a sensitive, robust, high-throughput method for quantifying the formation of micronuclei, markers of genome instability, in mouse erythrocytes. Micronuclei are whole chromosomes or chromosome segments that have been separated from the nucleus. Other methods of detection rely on labor-intensive, microscopy-based techniques. Here we describe a 2-d, 96-well plate–based flow cytometric method of micronucleus scoring that is simple enoughRead more
The p53 tumor suppressor gene encodes a homotetrameric transcription factor which is activated in response to a variety of cellular stressors, including DNA damage and oncogene activation. p53 mutations occur in >50% of human cancers. Although p53 has been shown to regulate Wnt signaling, the underlying mechanisms are not well understood. Here we show that silencing p53 in colon cancer cells led to increased expression of Aha1, a co-chaperone ofRead more
Genome instability is a feature of nearly all cancers and can be exploited for therapy. In addition, a growing number of genome maintenance genes have been associated with developmental disorders. Efforts to understand the role of genome instability in these processes will be greatly facilitated by a more comprehensive understanding of their genetic network. We highlight recent genetic screens in model organisms that have assisted in the discoveryRead more
The human genomic instability syndrome Ataxia Telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency, and increased cancer predisposition. ATM is central to a pathway that responds to double strand DNA breaks, while the related kinase ATR leads a parallel signaling cascade that is activated by replication stress. ToRead more
Steatoapoptosis is a hallmark of non-alcoholic fatty liver disease (NAFLD) and is an important factor in liver disease progression. We hypothesized that increased reactive oxygen species resulting from excess dietary fat contribute to liver disease by causing DNA damage and apoptotic cell death, and tested this by investigating the effects of feeding mice high fat or standard diets for 8 weeks. High fat diet feeding resulted in increased hepaticRead more