The Tim (Timeless)-Tipin complex has been proposed to maintain genome stability by facilitating ATR-mediated Chk1 activation. However, as a replisome component, Tim-Tipin has also been suggested to couple DNA unwinding to synthesis, an activity expected to suppress single-stranded DNA (ssDNA) accumulation and limit ATR-Chk1 pathway engagement. We now demonstrate that Tim-Tipin depletion is suff...

The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDro...

Cationic charged chitosan as stabilizer was evaluated in preparation of nanocrystals using probe sonication method. The influence of cationic charge densities of chitosan (low CS(L), medium CS(M), high CS(H) molecular weights) and Labrasol(®) in solubility enhancement and modifying the release was investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to CS(M) and CS(H); ...

What do ATM and ATR do in the cell? To maintain genomic stability in the face of constant exposure to exogenous and endogenous DNA-damaging agents, all eukaryotic cells contain elaborate, highly conserved pathways to sense, signal and repair DNA damage. ATM and ATR act near the top of these signalling networks. Their role here is so important that they have been described as ‘sentries at the ga...

Phonological studies of ATR harmony have led to advances in autosegmental phonology, markedness theory, and locality. Nevertheless, many of our theoretical assumptions may have been based on misanalyzed data or non-rigorous typological assumptions. For example, detailed acoustic and/or articulatory studies have shown that transparent vowels are not always transparent (Gick et al 2006, Richart &...

The ATR protein is a member of the phosphoinositide 3-kinase-related kinase family and plays an important role in UV-induced DNA damage checkpoint response. Its role as a signal transducer in cell cycle checkpoint is well established, but it is currently unclear whether ATR functions as a damage sensor as well. Here we have purified the ATR protein and investigated its interaction with DNA by u...

Infrared (IR) spectroscopy is used extensively to characterize the chemical composition of trace evidence such as paints, fibers and adhesives as well as seized drugs and related chemicals. We have recently introduced the Thermo ScientificTM iSTM50 ATR module, a novel, extended-range attenuated total reflectance (ATR) module that is integrated into the NicoletTM iS50 FT-IR spectrometer. This in...

UNLABELLED The ATR kinase has essential functions in maintenance of genome integrity in response to replication stress. ATR is recruited to RPA-coated single-stranded DNA at DNA damage sites via its interacting partner, ATRIP, which binds to the large subunit of RPA. ATR activation typically leads to activation of the Chk1 kinase among other substrates. We show here that, together with a number...

Hyperthermia is widely used to treat patients with cancer, especially in combination with other treatments such as radiation therapy. Heat treatment per se activates DNA damage responses mediated by the ATR-Chk1 and ATM-Chk2 pathways but it is not fully understood how these DNA damage responses are activated and affect heat tolerance. By performing a genetic analysis of human HeLa cells and chi...

Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is widely used as a broad-spectrum herbicide. Animal studies have demonstrated that ATR exposure can cause cell death in dopaminergic neurons. The molecular mechanisms underlying ATR-induced neuronal cell death, however, are unknown. In this study, we investigated the autophagy and apoptosis induced by ATR in dopaminergic ne...