Mismatch repair and repair of insertion/deletion loops in eukaryotic DNA

The mismatch repair (MMR) system detects non-Watson - Crick base pairs as well as the defects, appearing in course of DNA replication, and helps to eliminate them by catalyzing the excision of the defect-containing region of daughter DNA and its error-free resynthesis. Thus, MMR remarkably improves the fidelity of replication. After separation, both strands contain non-repairable damages and the mismatches may generate DnA mutation in 50 % of cell progeny after next replication. MMR dysfunction causes surge of mutation rate, abnormal recombination, and cancer in humans and animals. Therefore, the main MMR efficiency parameter is mismatch correction before the next replication cycle. Mismatch detection is made by the MSH2 protein, which forms a heterodimer with either MSH6 or MSH3 (Mut S), depending on the damage (MSH6 is needed for the amendment of single base mispairs, whereas both MSH3 and MSH6 can correct IDLs). A heterodimer of MLH1 and PMS2 (Mut L) controls the interaction between the mismatch-detecting complex of proteins and other proteins essential for MMR, including exonuclease 1, helicase, nuclear antigen of proliferating cells, single-stranded DNA-binding protein and DNA polymerases δ and ε. MLH1 can form a heterodimer with two additional proteins - MLH3 and PMS1. PMS2 is required for the correction of single based mismatches, and PMS2 and MLH3 contribute to the correction of IDLs. The Nobel Prize in Chemistry 2015 was awarded for the studies of DNA repair, i.a. MMR

Features of Chronic Bronchitis in Different Age Groups

Background: Lung diseases are assuming greater relevance and importance today. Chronic bronchitis is a self-nosology, which may precede the development of COPD, the importance of which can hardly be overestimated. The main problem in this disease is caused by late diagnosis and treatment due to the delay by patients in seeking medical help. The aim of the work was to study the distribution and exposure to tobacco smoke, especially chronic bronchitis, depending on various factors, including age. Methods: We examined 1779 persons, including 855 men and 924 women. The mean age of the population was 35.83±8.3 years. We conducted surveys and spirometry. The outcome was assessed after a bronchodilation test was performed with salbutamol 400 mcg. We performed all statistical analysis using software package Statistica 10. Results: We identified chronic bronchitis in 9.2% of the cases in the group of younger individuals and in 14.9% of the cases in the group of older individuals, during the active detection of chronic bronchitis using questionnaires. The prevalence of cigarette smoking was slightly higher among the younger (39.5%) than the older persons (33.6%); the frequency of smoking in a group of chronic bronchitis was reliably higher. Also, in this group, the performance spirometry reliably decreased. Conclusions: Outpatient survey is an effective method of identifying chronic bronchitis. Smoking is a major risk factor in the group of young respondents and the prevalence of smoking is inversely related to the education level of the respondents, regardless of age. As the decline in the Forced Expiratory Volume (FEV1 and FEV1/FVC) is the main criterion diagnosis of COPD, it revealed significant declines in the FEV1 of the younger smoking individuals, which may help to predict the development of COPD in the older age group