Multi-BRCT Domain Protein Brc1 Links Rhp18/Rad18 and γH2A To Maintain Genome Stability during S Phase.

DNA replication involves the inherent risk of genome instability, since replisomes invariably encounter DNA lesions or other structures that stall or collapse replication forks during the S phase. In the fission yeast , the multi-BRCT domain protein Brc1, which is related to budding yeast Rtt107 and mammalian PTIP, plays an important role in maintaining genome integrity and cell viability when cells experience replication stress. The C-terminal pair of BRCT domains in Brc1 were previously shown to bind phosphohistone H2A (γH2A) formed by Rad3/ATR checkpoint kinase at DNA lesions; however, the putative scaffold interactions involving the N-terminal BRCT domains 1 to 4 of Brc1 have remained obscure.

High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are maintained between the primary tumor and the patient-derived tumor models.

γH2A-binding protein Brc1 affects centromere function in fission yeast.

The coordinated replication and transcription of pericentromeric repeats enable RNA interference (RNAi)-mediated transmission of pericentromeric heterochromatin in fission yeast, which is essential for the proper function of centromeres. Rad3/ATR kinase phosphorylates histone H2A on serine-128/-129 to create γH2A in pericentromeric heterochromatin during S phase, which recruits Brc1 through its breast cancer gene 1 protein (BRCA1) C-terminal (BRCT) domains. Brc1 prevents the collapse of stalled replication forks; however, it is unknown whether this activity influences centromere function.

Replication fork collapse and genome instability in a deoxycytidylate deaminase mutant.

Ribonucleotide reductase (RNR) and deoxycytidylate deaminase (dCMP deaminase) are pivotal allosteric enzymes required to maintain adequate pools of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis and repair. Whereas RNR inhibition slows DNA replication and activates checkpoint responses, the effect of dCMP deaminase deficiency is largely unknown. Here, we report that deleting the Schizosaccharomyces pombe dcd1(+) dCMP deaminase gene (SPBC2G2.

Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing.

Ultra-deep targeted sequencing (UDT-Seq) can identify subclonal somatic mutations in tumor samples. Early assays' limited breadth and depth restrict their clinical utility. Here, we target 71 kb of mutational hotspots in 42 cancer genes.

Rad3 decorates critical chromosomal domains with gammaH2A to protect genome integrity during S-Phase in fission yeast.

Schizosaccharomyces pombe Rad3 checkpoint kinase and its human ortholog ATR are essential for maintaining genome integrity in cells treated with genotoxins that damage DNA or arrest replication forks. Rad3 and ATR also function during unperturbed growth, although the events triggering their activation and their critical functions are largely unknown. Here, we use ChIP-on-chip analysis to map genomic loci decorated by phosphorylated histone H2A (gammaH2A), a Rad3 substrate that establishes a chromatin-based recruitment platform for Crb2 and Brc1 DNA repair/checkpoint proteins.

Morphological control and assembly of zinc oxide using a biotemplate.

Zinc oxide is a wide band gap material that has significant applications in photovoltaics, piezoelectrics and optoelectronics. Traditionally, ZnO has been synthesized using high temperatures and harsh reaction conditions. Recently, benign reaction conditions have been used to synthesize ZnO using amine and citrate additives.

Protection of telomeres by a conserved Stn1-Ten1 complex.

Telomeres are specialized chromatin structures that protect chromosome ends. Critical among telomere proteins are those that bind the telomeric single-strand DNA (ssDNA) overhangs. These proteins are thought to differ among eukaryotes.

Characterization of microbial contamination in United States Air Force aviation fuel tanks.

Bacteria and fungi, isolated from United States Air Force (USAF) aviation fuel samples, were identified by gas chromatograph fatty acid methyl ester (GC-FAME) profiling and 16S or 18S rRNA gene sequencing. Thirty-six samples from 11 geographically separated USAF bases were collected. At each base, an above-ground storage tank, a refueling truck, and an aircraft wing tank were sampled at the lowest sample point, or sump, to investigate microbial diversity and dispersion within the fuel distribution chain.

Cellular internalization and targeting of semiconductor quantum dots.

Peptide-mediated internalization and organelle targeting of quantum dots.