RESUMEN
Transcription-coupled DNA repair (TCR) is presumed to be a minor sub-pathway of nucleotide excision repair (NER) in bacteria. Global genomic repair is thought to perform the bulk of repair independently of transcription. TCR is also believed to be mediated exclusively by Mfd-a DNA translocase of a marginal NER phenotype1-3. Here we combined in cellulo cross-linking mass spectrometry with structural, biochemical and genetic approaches to map the interactions within the TCR complex (TCRC) and to determine the actual sequence of events that leads to NER in vivo. We show that RNA polymerase (RNAP) serves as the primary sensor of DNA damage and acts as a platform for the recruitment of NER enzymes. UvrA and UvrD associate with RNAP continuously, forming a surveillance pre-TCRC. In response to DNA damage, pre-TCRC recruits a second UvrD monomer to form a helicase-competent UvrD dimer that promotes backtracking of the TCRC. The weakening of UvrD-RNAP interactions renders cells sensitive to genotoxic stress. TCRC then recruits a second UvrA molecule and UvrB to initiate the repair process. Contrary to the conventional view, we show that TCR accounts for the vast majority of chromosomal repair events; that is, TCR thoroughly dominates over global genomic repair. We also show that TCR is largely independent of Mfd. We propose that Mfd has an indirect role in this process: it participates in removing obstructive RNAPs in front of TCRCs and also in recovering TCRCs from backtracking after repair has been completed.
Asunto(s)
Proteínas Bacterianas , Reparación del ADN , Escherichia coli , Transcripción Genética , Adenosina Trifosfatasas , Bacterias/genética , Proteínas Bacterianas/genética , Daño del ADN , ADN Helicasas , Proteínas de Unión al ADN , ARN Polimerasas Dirigidas por ADN/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coliRESUMEN
This study aimed to evaluate the nutritional status and associated risk factors of Syrian children living in Saudi Arabia. In this study, 55 boys and 55 girls ranging in age from 6 to 12 years were selected. Socioeconomic data of families were collected using a structured questionnaire. The participants' anthropometric measurements were calculated. The 24-h recall method was applied to calculate the daily food intake. Dietary nutrients' average daily intake of both boys and girls was significantly (p ≤ 0.01) lower than that of the dietary reference intake (DRI) with few exceptions. The sedentary lifestyles of both boys and girls had a negative impact on their food choices, and as a result, a large number of them were underweight and suffered from malnutrition and stunting. Spearman correlation coefficients revealed that most of the children's dependent variables were risk factors and strongly and negatively associated with their nutritional status proxies. The study concluded that both boys and girls had unbalanced nutritional status with high percentages of malnutrition and stunting because most dependent factors were adversely related to the independent ones.