112 research outputs found
Structure and mechanism of human DNA polymerase η
The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites
INTESTINAL AND PULMONARY INFECTION BY Cryptosporidium parvum IN TWO PATIENTS WITH HIV/AIDS
Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress
Exploring the nonlinear relationship between body mass index and health-related quality of life among adults: a cross-sectional study in Shaanxi Province, China
Prevalence and clinical features of celiac disease in patients with autoimmune thyroiditis: cross-sectional study
Uso de medidas autorreferidas de peso e altura na determinação do estado nutricional de trabalhadores
Clinical characteristics associated with hepatic steatosis on ultrasonography in patients with elevated alanine aminotransferase
Phosphomannose isomerase affects the key enzymes of glycolysis and sucrose metabolism in transgenic sugarcane overexpressing the manA gene
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