WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases.

Purified translesion synthesis (TLS) DNA polymerases (Pols) replicate through DNA lesions with a low fidelity; however, TLS operates in a predominantly error-free manner in normal human cells. To explain this incongruity, here we determine whether Y family Pols, which play an eminent role in replication through a diversity of DNA lesions, are incorporated into a multiprotein ensemble and whether the intrinsically high error rate of the TLS Pol is ameliorated by the components in the ensemble. To this end, we provide evidence for an indispensable role of Werner syndrome protein (WRN) and WRN-interacting protein 1 (WRNIP1) in Rev1-dependent TLS by Y family Polη, Polι, or Polκ and show that WRN, WRNIP1, and Rev1 assemble together with Y family Pols in response to DNA damage.

Transcript-specific induction of stop codon readthrough using a CRISPR-dCas13 system.

Stop codon readthrough (SCR) is the process where translation continues beyond a stop codon on an mRNA. Here, we describe a strategy to enhance or induce SCR in a transcript-selective manner using a CRISPR-dCas13 system. Using specific guide RNAs, we target dCas13 to the region downstream of canonical stop codons of mammalian AGO1 and VEGFA mRNAs, known to exhibit natural SCR.

A novel role of DNA polymerase λ in translesion synthesis in conjunction with DNA polymerase ζ.

By extending synthesis opposite from a diverse array of DNA lesions, DNA polymerase (Pol) ζ performs a crucial role in translesion synthesis (TLS). In yeast and cancer cells, Rev1 functions as an indispensable scaffolding component of Polζ and it imposes highly error-prone TLS upon Polζ. However, for TLS that occurs during replication in normal human cells, Rev1 functions instead as a scaffolding component of Pols η, ι, and κ and Rev1-dependent TLS by these Pols operates in a predominantly error-free manner.

Induction of Translational Readthrough across the Thalassemia-Causing Premature Stop Codon in β-Globin-Encoding mRNA.

Nonsense mutations that result in premature stop codons in the gene cause β-thalassemia. This disease is characterized by a reduced hemoglobin level due to the lack of β-globin. Compounds that induce translational readthrough across the thalassemia-causing premature stop codon will have therapeutic benefits.

Mutational spectrum and identification of five novel mutations in G6PC1 gene from a cohort of Glycogen Storage Disease Type 1a.

Background: Glycogen storage disease type-1a is an inherited, autosomal recessive disorder caused by mutations in G6PC1 gene leading to deficiency of glucose-6-phosphatase-α specifically in the liver/kidney/intestine.

Patients And Methods: DNA of six unrelated Indian GSD-1a patients were screened for mutations in the entire coding region of G6PC1 gene followed by direct DNA sequencing and functional was tested using glucose-6-phosphatase assay.

Results: Mutational screening of GSD-1a patients identified five novel mutations, viz.

Coordination geometry-induced optical imaging of l-cysteine in cancer cells using imidazopyridine-based copper(ii) complexes.

Overexpression of cysteine cathepsins proteases has been documented in a wide variety of cancers, and enhances the l-cysteine concentration in tumor cells. We report the synthesis and characterization of copper(ii) complexes [Cu(L1)(HO)](SOCF), 1, L1 = 3-phenyl-1-(pyridin-2-yl)imidazo[1,5-a]pyridine, [Cu(L2)(SOCF)]SOCF, 2, L2 = 3-(4-methoxyphenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine, [Cu(L3)(HO)](SOCF), 3, L3 = 3-(3,4-dimethoxy-phenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine and [Cu(L4)(HO)](SOCF), 4, L4 = dimethyl-[4-(1-pyridin-2-yl-imidazo[1,5-a]pyridin-3-yl)phenyl]amine as 'turn-on' optical imaging probes for l-cysteine in cancer cells. The molecular structure of complexes adopted distorted trigonal pyramidal geometry (τ, 0.

Stimulation of angiogenesis using single-pulse low-pressure shock wave treatment.

Endothelial cells respond to mechanical stimuli such as stretch. This property can be exploited with caution to induce angiogenesis which will have immense potential to treat pathological conditions associated with insufficient angiogenesis. The primary aim of this study is to test if low-pressure shock waves can be used to induce angiogenesis.

Adaptive regulation of riboflavin transport in heart: effect of dietary riboflavin deficiency in cardiovascular pathogenesis.

Deficiency or defective transport of riboflavin (RF) is known to cause neurological disorders, cataract, cardiovascular anomalies, and various cancers by altering the biochemical pathways. Mechanisms and regulation of RF uptake process is well characterized in the cells of intestine, liver, kidney, and brain origin, while very little is known in the heart. Hence, we aimed to understand the expression and regulation of RF transporters (rRFVT-1 and rRFVT-2) in cardiomyocytes during RF deficiency and also investigated the role of RF in ischemic cardiomyopathy and mitochondrial dysfunction in vivo.

A novel antimicrobial therapy for the control of Aeromonas hydrophila infection in aquaculture using marine polysaccharide coated gold nanoparticle.

In the present study, we prepared fucoidan coated Au-NPs (Fu-AuNPs), and examined its antimicrobial activity against Aeromonas hydrophila. The green synthesized Fu-AuNPs were bio-physically characterized by Ultraviolet-visible (UV-Vis) spectroscopy, X-ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), Higher Transmission Electron Microscopy (HR-TEM), Zeta potential analysis and Energy Dispersive X-ray spectroscopy (EDX). Fu-AuNPs were crystalline in nature, spherical to triangular in shape, with particle size ranging within 10-100 nm.

3'-UTR SNP rs2229611 in G6PC1 affects mRNA stability, expression and Glycogen Storage Disease type-Ia risk.

The frequency of rs2229611, previously reported in Chinese, Caucasians, Japanese and Hispanics, was investigated for the first time in Indian ethnicity. We analyzed its role in the progression of Glycogen Storage Disease type-Ia (GSD-Ia) and breast cancer. Genotype data on rs2229611 revealed that the risk of GSD-Ia was higher (P=0.

Novel nonsense mutation (p.Ile411Metfs*12) in the SLC19A2 gene causing Thiamine Responsive Megaloblastic Anemia in an Indian patient.

Thiamine-responsive megaloblastic anemia (TRMA), an autosomal recessive disorder, is caused by mutations in SLC19A2 gene encodes a high affinity thiamine transporter (THTR-1). The occurrence of TRMA is diagnosed by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Here, we report a female TRMA patient of Indian descent born to 4th degree consanguineous parents presented with retinitis pigmentosa and vision impairment, who had a novel homozygous mutation (c.

Riboflavin transporter-2 (rft-2) of Caenorhabditis elegans: Adaptive and developmental regulation.

Riboflavin transporters (rft-1 and rft-2), orthologous to human riboflavin transporter-3 (hRVFT-3), are identified and characterized in Caenorhabditis elegans. However, studies pertaining to functional contribution of rft-2 in maintaining body homeostatic riboflavin levels and its regulation are very limited. In this study, the expression pattern of rft-2 at different life stages of C.