A5061104556- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Enzyme Structure and Function
- Cancer Genomics and Diagnostics
- COVID-19 Clinical Research Studies
- Genetic Neurodegenerative Diseases
- Melanoma and MAPK Pathways
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Cancer-related Molecular Pathways
- Tryptophan and brain disorders
- Acute Lymphoblastic Leukemia research
- Ovarian cancer diagnosis and treatment
- Bacterial Genetics and Biotechnology
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Advanced Glycation End Products research
University of California, Davis
2012-2024
University of California Davis Medical Center
2021
Lawrence Berkeley National Laboratory
2020
The base excision repair glycosylase MUTYH prevents mutations associated with the oxidatively damaged base, 8-oxo-7,8-dihydroguanine (OG), by removing undamaged misincorporated adenines from OG:A mispairs. Defects in individuals inherited variants are correlated colorectal cancer predisposition syndrome known as MUTYH-associated polyposis (MAP). Herein, we reveal key structural features of OG required for efficient human using structure–activity relationships (SAR). We developed a GFP-based...
Xeroderma pigmentosum group G (XPG) protein is both a functional partner in multiple DNA damage responses (DDR) and pathway coordinator structure-specific endonuclease nucleotide excision repair (NER). Different mutations the XPG gene ERCC5 lead to either of two distinct human diseases: Cancer-prone xeroderma (XP-G) or fatal neurodevelopmental disorder Cockayne syndrome (XP-G/CS). To address enigmatic structural mechanism for these differing disease phenotypes XPG’s role DDRs, here we...
An inherited deficiency in the frataxin protein causes neurodegeneration of dorsal root ganglia and Friedreich's ataxia (FA). Frataxin leads to oxidative stress inflammatory changes cell animal models; however, cause changes, especially what brain microglial activation is unclear. Here we investigated: 1) mechanism by which activates microglia, 2) whether a brain-localized stimulus provokes greater response FA models, 3) an anti-inflammatory treatment improves their condition....
Biallelic germline mutations in the base excision repair enzyme gene MUTYH lead to multiple colorectal adenomas and carcinomas referred as MUTYH-associated polyposis.MUTYH removes adenine misincorporated opposite DNA oxidation product, 8-oxoguanine (OG), thereby preventing accumulation of G:C T:A transversion mutations.The most common cancer-associated variant proteins when expressed bacteria exhibit reduced OG:A mismatch affinity removal activity.However, direct evaluation efficiency...
Abstract Background TP53 mutations occur in more than 50% of cancers. We sought to determine the effect intragenic P72R single nucleotide polymorphism (SNP; rs1042522) on oncogenic properties mutant p53. Methods allelic selection tumors was determined from genotype calls and a Gaussian distributed mixture model. The SNP p53 p53-negative cancer cell lines. RNA-sequencing, chromatin immunoprecipitation, survival analysis were performed describe effect. All statistical tests 2-sided. Results...
Mammalian MutY glycosylases have a unique architecture that features an interdomain connector (IDC) joins the catalytic N-terminal domain and 8-oxoguanine (OG) recognition C-terminal domain. The IDC has been shown to be hub for interactions with protein partners involved in coordinating downstream repair events signaling apoptosis. Herein, previously unidentified zinc ion its coordination by three Cys residues of region eukaryotic organisms were characterized mutagenesis, ICP-MS, EXAFS. In...
Higher expression of the human DNA repair enzyme MUTYH has previously been shown to be strongly associated with reduced survival in a panel 24 lymphoblastoid cell lines exposed alkylating agent <i>N</i>-methyl-<i>N</i>′-nitro-<i>N</i>-nitrosoguanidine (MNNG). The molecular mechanism MUTYH-enhanced MNNG cytotoxicity is unclear, because well-established role oxidative lesions. Here, we show mouse embryonic fibroblasts (MEFs) that this MNNG-dependent phenotype does not involve damage and occurs...