Medicine and Health Sciences Commons^™

Exposure Of Human Lung Cells To Tobacco Smoke Condensate Inhibits The Nucleotide Excision Repair Pathway, Nathaniel C. Holcomb, Mamta Goswami, Sung Gu Han, Samuel Clark, David K. Orren, C. Gary Gairola, Isabel Mellon

Toxicology and Cancer Biology Faculty Publications

Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER) pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC), a surrogate for tobacco smoke, …

Ubiquitin-Specific Peptidase 10 (Usp10) Deubiquitinates And Stabilizes Muts Homolog 2 (Msh2) To Regulate Cellular Sensitivity To Dna Damage, Mu Zhang, Chen Hu, Dan Tong, Shengyan Xiang, Kendra Williams, Wenlong Bai, Guo-Min Li, Gerold Bepler, Xiaohong Zhang

Toxicology and Cancer Biology Faculty Publications

MSH2 is a key DNA mismatch repair protein, which plays an important role in genomic stability. In addition to its DNA repair function, MSH2 serves as a sensor for DNA base analogs-provoked DNA replication errors and binds to various DNA damage-induced adducts to trigger cell cycle arrest or apoptosis. Loss or depletion of MSH2 from cells renders resistance to certain DNA-damaging agents. Therefore, the level of MSH2 determines DNA damage response. Previous studies showed that the level of MSH2 protein is modulated by the ubiquitin-proteasome pathway, and histone deacetylase 6 (HDAC6) serves as an ubiquitin E3 ligase. However, the deubiquitinating …

Identification Of An Association Of Tnfaip3 Polymorphisms With Matrix Metalloproteinase Expression In Fibroblasts In An Integrative Study Of Systemic Sclerosis-Associated Genetic And Environmental Factors.*, Peng Wei, Yang Yang, Xinjian Guo, Nainan Hei, Syeling Lai, Shervin Assassi, Mengyuan Liu, Filemon Tan, Xiaodong Zhou

Faculty Publications

OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.

METHODS: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis …