Heat shock protein 90 (Hsp90) is an evolutionary conserved molecular chaperone that, together with Hsp70 and co-chaperones makes up the Hsp90 chaperone machinery, stabilizing and activating more than 200 proteins, involved in protein homeostasis (i.e., proteostasis), transcriptional regulation, chromatin remodeling, and DNA repair. Cells respond to DNA damage by activating complex DNA damage re...

OBJECTIVES The aims of this study were to assess expressions of the DNA damage response (DDR)-related proteins and to investigate their clinical significances in gastric carcinoma. METHODS Two independent cohorts, a training set (n=524) and validation set (n=394), of gastric cancer patients were enrolled. Ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions wer...

Small RNA-mediated gene silencing pathways play important roles in the regulation of development, genome stability and various stress responses in many eukaryotes. Recently, a new type of small interfering RNAs (qiRNAs) approximately 20-21 nucleotides long in Neurospora crassa have been shown to mediate gene silencing in the DNA damage response (DDR) pathway. However, the mechanism for RNA sile...

This paper identifies major future trends and driving factors and perspectives and challenges resulting from them for European agriculture and food sectors until the year 2020. The focus of the paper is an analysis of key driving forces and the provision of a well developed reference scenario under the assumption of continued CAP reform and taking into account the framework discussions in the D...

Human parvovirus B19 (B19V) infection is highly restricted to human erythroid progenitor cells, in which it induces a DNA damage response (DDR). The DDR signaling is mainly mediated by the ATR (ataxia telangiectasia-mutated and Rad3-related) pathway, which promotes replication of the viral genome; however, the exact mechanisms employed by B19V to take advantage of the DDR for virus replication ...

Telomeres are by definition stable and inert chromosome ends, whereas internal chromosome breaks are potent stimulators of the DNA damage response (DDR). Telomeres do not, as might be expected, exclude DDR proteins from chromosome ends but instead engage with many DDR proteins. However, the most powerful DDRs, those that might induce chromosome fusion or cell-cycle arrest, are inhibited at telo...

Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins, including CBX4, have been shown to accumulate at sites of DNA damage. However, it remains unclear whether or not CBX4 or its E3 sumo ligase activity ...

The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveillance system, the DNA damage response (DDR) pathway, which maintains genetic integrity. In additi...

Based on Basque data (and in line with Etxeberria & Giannakidou 2010, to appear), this paper argues that the domain for quantifiers in certain languages is restricted overtly by a definite determiner (D). This strategy of domain restriction via D—DDR—happens by applying DDR to the nominal argument, but DDR can also apply to the Q-det itself, in which case it forms a constituent with it. In both...

We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28...