DNA replication in eukaryotes is asymmetric, with separate DNA polymerases (Pol) dedicated to bulk synthesis of the leading and lagging strands. Pol α/primase initiates primers on both strands that are extended by Pol e on the leading strand and by Pol δ on the lagging strand. The CMG (Cdc45-MCM-GINS) helicase surrounds the leading strand and is proposed to recruit Pol e for leading-strand synt...

Tumors defective for DNA polymerase (Pol) e proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol e proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered t...

The problem-oriented learning (POL) paradigm has been successfully implemented in electronic medical teaching. Several e-learning and authoring platforms for POL are available. At the Freiburg University Hospital an interdisciplinary POL program has been established in the domain of Neuro-Oncology (OncoCase) utilizing the Campus e-learning platform. OncoCase e-learning is in the process of bein...

We have purified a DNA polymerase activity from 0to 2-hr embryos of Drosophila melanogaster to near homogeneity. The purified enzyme consists of a single 120-kDa polypeptide, which contains polymerase and 3'-.5' exonuclease activities. Exonuclease activity is inhibited by deoxynucleoside triphosphates, suggesting that the polymerase and exonuclease activities are coupled. The polymerase is more...

Asymptomatic bacteriuria (ABU) is a bacterial carrier state in the urinary tract that resembles commensalism at other mucosal sites. ABU strains often lack the virulence factors that characterize uropathogenic Escherichia coli (E. coli) strains and therefore elicit weak innate immune responses in the urinary tract. In addition, ABU strains are active modifiers of the host environment, which the...

The damage-inducible UmuD' and UmuC proteins are required for most SOS mutagenesis in Escherichia coli. Our recent assay to reconstitute this process in vitro, using a native UmuD'(2)C complex, revealed that the highly purified preparation contained DNA polymerase activity. Here we eliminate the possibility that this activity is caused by a contaminating DNA polymerase and show that it is intri...

Despite their high frequency of RNA recombination, the plus-strand coronaviruses have a characteristic, strictly conserved genome organization with the essential genes occurring in the order 5'-polymerase (pol)-S-E-M-N-3'. We have investigated the significance of this remarkable conservation by rearrangement of the murine coronavirus genome through targeted recombination. Thus, viruses were pre...

During the past decade, five DNA polymerases (pol) have been characterized in eukaryotic cells. These enzymes are called a, p, y, 6, and E (Wang 1991). Their enzymatic properties, protein composition and structure, effectors, genetic relationships, genomic locations, expression during cell growth and proliferation, and their roles in DNA replication and repair have been described in previous re...