Replication Protein A (RPA) Hampers the Processive Action of APOBEC3G Cytosine Deaminase on Single-Stranded DNA

deamination assays and expression of A3G in yeast, we show that replication protein A (RPA), the eukaryotic single-stranded DNA (ssDNA) binding protein, severely inhibits the deamination activity and processivity of A3G. on long ssDNA regions. This resembles the “hit and run” single base substitution events observed in yeast., we propose that RPA plays a role in the protection of the human genome cell from A3G and other deaminases when they are inadvertently diverged from their natural targets. We propose a model where RPA serves as one of the guardians of the genome that protects ssDNA from the destructive processive activity of deaminases by non-specific steric hindrance

Estimating the Thermochemistry of Adsorbates Based Upon Gas-Phase Properties

A method for estimating the enthalpy, entropy, and heat capacity for adsorbates on metals is presented. The only input parameters are the binding energy of the adsorbate and the geometric properties of the gas-phase precursor. The method assumes that the vibrational frequencies of the metal lattice and the gas-phase precursor are conserved upon adsorption. Six “rules of thumb” are presented to estimate the new vibrational frequencies that correspond to the loss of external translation and rotation upon adsorption. The method is tested against density functional theory calculations for 17 species and 36 reversible reactions for methane steam reforming on Ni(111)[3]. The heats of adsorption and heats of reaction at 800 °C are correctly predicted to within 1 kcal/mol. The entropy of reaction is less accurate, with an average deviation of 3.1 cal/mol/K, but in the context of rapid development for thermodynamically consistent mechanisms and computational catalyst screening for high-temperature applications, this error may be tolerable

Platin-related Hearing Loss: Further Results from PanCareLIFE

Background: Cisplatin and Carboplatin are widely-used in paediatric cancer treatment. Sensorineural hearing loss (SNHL) is one long-term side-effect. This study utilises a larger sample than previous research in order to investigate risk-factors for platin-related ototoxicity.Material and methods: Retrospective audiological and treatment data of 997 children and adolescents were gathered with the involvement of 18 pan-European institutions in 7 different countries as part of the PanCareLIFE consortium. Prior hearing loss was excluded. Conductive hearing losses were excluded where identified.Results: Prevalence rates of clinically-significant hearing loss (=> 2b Münster Classification) after treatment were 49 % (Cisplatin) and 15 % (Carboplatin). Where Cisplatin was administered prior to Carboplatin, prevalence rose to 76 %. Frequencies in the high and extended high-frequency range were predominantly affected, with mean threholds between 25-35 dB HL. Mean thresholds at frequencies below 3 kHz remained lower than 20 dB HL. No significant air-bone gap was apparent.50 % of clinically-significant hearing losses began within 3 years of start of treatment (Kaplan-Meier analysis). No significant difference in time-to-onset at different frequencies within the standard range was found. Further analyses, including multifactorial analysis to account for platin doses, presence of cranial radiotherapy, age and date of diagnosis will be conducted.Discussion: Analysis of this large sample was able to confirm the significant risk of SNHL posed by platin-based chemotherapeutics. Some quantitative and qualitative variation were present in this multi-centre retrospective dataset.Conclusion: This large sample confirms that platin-based chemotherapeutics, especially cisplatin, pose a significant risk of SNHL and underlines the necessity of audiological monitoring during and after end of chemotherapy.Acknowledgement: This work was supported by the PanCareLIFE consortium that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030