Anti-RPA2 (aa 1-172) polyclonal antibody

Proper resolution of stalled replication forks is essential for genome stability. Purification of FBH1, a UvrD DNA helicase, identified a physical interaction with replication protein A (RPA), the major cellular single-stranded DNA (ssDNA)-binding protein complex. Compared with control cells, FBH1-depleted cells responded to replication stress with considerably fewer double-strand breaks (DSBs), a dramatic reduction in the activation of ATM and DNA-PK and phosphorylation of RPA2 and p53, and a significantly increased rate of survival. A minor decrease in ssDNA levels was also observed. All these phenotypes were rescued by wild-type FBH1, but not a FBH1 mutant lacking helicase activity. FBH1 depletion had no effect on other forms of genotoxic stress in which DSBs form by means that do not require ssDNA intermediates. In response to catastrophic genotoxic stress, apoptosis prevents the persistence and propagation of DNA lesions. Our findings show that FBH1 helicase activity is required for the efficient induction of DSBs and apoptosis specifically in response to DNA replication stress.

Objective: To evaluate the effect of regular physical activity (RPA) on the control of glycemia (glycosylated hemoglobin A(1c) level) and the frequency of severe hypoglycemia in a large cohort of patients with type 1 diabetes mellitus. Design: Cross-sectional analysis of data for 19143 patients, comparing control of glycemia and rate of hypoglycemia by frequency of RPA. Setting: One hundred seventy-nine pediatric diabetes clinics in Germany and Austria. Participants: Patients aged 3 to 20 years with type 1 diabetes mellitus. Main Exposure: Patients were grouped by the frequency of RPA per week as follows: RPA0, none; RPA1, 1 or 2 times per week; and RPA2, 3 or more times per week. Main Outcome Measures: Glycosylated hemoglobin A1c level, body mass index (calculated as weight in kilograms divided by the square of height in meters) z score, and frequency of severe hypoglycemia. Results: Glycosylated hemoglobin A(1c) level was higher in the groups with less frequent RPA (8.4% in group RPA0 vs 8.1% in group RPA2; P <. 001). This effect was found in both sexes and in all age groups (P <.001). In female patients but not in male patients, the body mass index z score decreased from 0.60 in group RPA0 to 0.51 in group RPA2 (P <.001). Multiple regression analysis revealed that RPA was one of the most important factors influencing the glycosylated hemoglobin level. No association was noted between frequency of RPA and frequency of severe hypoglycemia or hypoglycemia with loss of consciousness or seizure. Conclusions: In pediatric patients with type 1 diabetes mellitus, frequency of RPA is a major factor influencing the control of glycemia without increasing the risk for severe hypoglycemia. Regular physical activity should be recommended in pediatric patients with type 1 diabetes mellitus.