A5060417615- Amyotrophic Lateral Sclerosis Research
- DNA Repair Mechanisms
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Antifungal resistance and susceptibility
- Fungal and yeast genetics research
- Cancer-related Molecular Pathways
- Parkinson's Disease Mechanisms and Treatments
- Microtubule and mitosis dynamics
- Cancer therapeutics and mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Molecular Biology Techniques and Applications
- Enzyme Structure and Function
- Histone Deacetylase Inhibitors Research
- Genetic Neurodegenerative Diseases
- Ubiquitin and proteasome pathways
- Fungal Infections and Studies
- Prion Diseases and Protein Misfolding
- bioluminescence and chemiluminescence research
- Neuroinflammation and Neurodegeneration Mechanisms
- Mycotoxins in Agriculture and Food
- Probiotics and Fermented Foods
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
Houston Methodist
2019-2024
Institute of Life Sciences
2015-2021
Abstract TAR DNA-binding protein 43 (TDP43) is increasingly recognized for its involvement in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP43 proteinopathy, characterized by dysregulated nuclear export cytoplasmic aggregation, present most ALS/FTD cases associated with a loss of function genomic instability neurons. Building on prior evidence linking pathology to DNA double-strand breaks (DSBs), this study identifies novel...
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the motor neuron. One aspect of neuropathology involved in ALS includes increased genomic damage and impaired DNA repair capability. The TAR-DNA binding protein 43 (TDP43) has been associated with both sporadic familial forms ALS, typically observed as cytosolic mislocalization aggregates, termed TDP43 proteinopathy. ubiquitous RNA/DNA functional implications wide range processes, including...
Abstract Mitochondrial dysfunction is a central aspect of Parkinson’s disease (PD) pathology, yet the underlying mechanisms are not fully understood. This study investigates link between α-Synuclein (α-Syn) pathology and loss translocase outer mitochondrial membrane 40 (TOM40), unraveling its implications for dysfunctions in neurons. We discovered that TOM40 protein depletion occurs brains patients with Guam Parkinsonism-Dementia (Guam PD) cultured neurons expressing α-Syn proteinopathy,...
Proliferating cell nuclear antigen (PCNA/POL30) an essential protein forms a homotrimeric ring encircling dsDNA and serves as molecular scaffold to recruit various factors during DNA replication, repair recombination. According Candida Genome Database (CGD), orf19.4616 sequence is predicted encode C. albicans PCNA (CaPCNA) that has not been characterized yet. Molecular modeling studies of using S. cerevisiae (ScPCNA) template, its subsequent biochemical characterizations suggest like other...
DNA–protein cross-links (DPCs) are toxic DNA lesions that interfere with metabolic processes such as replication, transcription, and recombination. USP11 deubiquitinase participates in repair, but the role of DPC repair is not known. SPRTN a replication-coupled DNA-dependent metalloprotease cleaves proteins cross-linked to promote repair. function tightly regulated by monoubiquitin switch controls auto-proteolysis chromatin accessibility during Previously, VCPIP1 USP7 deubiquitinases have...
Human DNA polymerase delta (Polδ), a holoenzyme consisting of p125, p50, p68, and p12 subunits, plays an essential role in replication, repair, recombination. Herein, using multiple physicochemical cellular approaches, we found that the protein forms dimer solution. In vitro reconstitution pull down Polδ by tagged substantiate pentameric nature this critical holoenzyme. Furthermore, consensus proliferating nuclear antigen (PCNA) interaction motif at extreme carboxyl-terminal tail...
Deletion of DNA polymerase eta (Rad30/Polη) in pathogenic yeast Candida albicans is known to reduce filamentation induced by serum, ultraviolet, and cisplatin. Because nonfilamentous C. widely accepted as avirulent form, here we explored the virulence pathogenicity a rad30Δ strain cell-based animal systems. Flow cytometry cocultured fungal differentiated macrophage cells revealed that comparatively higher percentage macrophages was associated with wild-type than cells. In contrast, number...
Fused-in sarcoma (FUS) gene mutations have been implicated in amyotrophic lateral sclerosis (ALS). This study aimed to investigate the impact of FUS (R521H and P525L) on transcriptome induced pluripotent stem cells (iPSCs) iPSC-derived motor neurons (iMNs). Using RNA sequencing (RNA Seq), we characterized differentially expressed genes (DEGs) lncRNAs (DELs) subsequently predicted lncRNA–mRNA target pairs (TAR pairs). Our results show that significantly altered expression profiles mRNAs...
Abstract TDP-43 mislocalization and aggregation are key pathological features of motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). However, existing overexpression animal models typically capture late-stage proteinopathies, leaving a gap in our understanding early neuron-specific disease mechanisms during pre-symptomatic phases. We address this by generating new endogenous knock-in (KI) mouse model using combination CRISPR/Cas9 FLEX...
Abstract Mitochondrial dysfunction is a central aspect of Parkinson's disease (PD) pathology, yet the underlying mechanisms are not fully understood. This study investigates link between α-Synuclein (α-Syn) pathology and loss translocase outer mitochondrial membrane 40 (TOM40), unraveling its implications for dysfunctions in neurons. We discovered that TOM40 protein depletion occurs brains patients with Guam Parkinsonism Dementia (Guam PD) cultured neurons expressing α-Syn proteinopathy,...
Abstract TDP-43 mislocalization and aggregation are key pathological features of motor neuron diseases (MND) including amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). However, transgenic hTDP-43 WT or ∆NLS-overexpression animal models mainly capture late-stages proteinopathy, do not provide a complete understanding early neuron-specific pathology during pre-symptomatic phases. We have now addressed this shortcoming by generating new endogenous knock-in (KI) mouse model...
Polη, a unique TLS DNA polymerase that promotes efficient bypass of UV-induced CPDs and cisplatin adducts, has not been explored in Candida species yet. Here, we show CaPolη plays vital role protecting albicans genome from diverse array damaging agents, limited to UV cisplatin. Polη deficient strain did exhibit any hyphal development the presence while wild type profusely developed damage induced filamentation. The polarized growth by HU MMS was found be independent. No common regulatory...
Abstract Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that has been linked to defective DNA repair. Many familial ALS patients harbor autosomal dominant mutations in the gene encoding RNA/DNA binding protein ‘fused sarcoma’ (FUS) commonly inducing its cytoplasmic mislocalization. Recent reports from our group and others demonstrate role of FUS maintaining genome integrity damage response (DDR). interacts with many DDR proteins may regulate their recruitment at...
Eukaryotic proliferating cell nuclear antigen (PCNA) plays an essential role in orchestrating the assembly of replisome complex, stimulating processive DNA synthesis, and recruiting other regulatory proteins during damage response. PCNA its binding partner network are relatively conserved eukaryotes, it exhibits extraordinary structural similarity across species. However, despite this similarity, a given species is rarely functional heterologous systems. In report, we determined X-ray...
DNA polymerase eta (Polη) is a unique translesion synthesis (TLS) enzyme required for the error-free bypass of ultraviolet ray (UV)-induced cyclobutane pyrimidine dimers in DNA. Therefore, its deficiency confers cellular sensitivity to UV radiation and an increased rate UV-induced mutagenesis. Polη possesses ubiquitin-binding zinc finger (ubz) domain PCNA-interacting-protein (pip) motif carboxy-terminal region. The role pip PCNA interaction recruitment stalled replication fork has been...
Abstract Genomic instability in Candida albicans is believed to play a crucial role fungal pathogenesis. DNA polymerases contribute significantly stability of any genome. Although Genome database predicts presence S. cerevisiae polymerase orthologs; functional and structural characterizations are still unexplored. eta (Polη) unique as it promotes efficient bypass cyclobutane pyrimidine dimers. Interestingly, C. heterozygous carrying two Polη genes the nucleotide substitutions were found only...
Fused-in Sarcoma (FUS) gene mutations have been implicated in amyotrophic lateral sclerosis (ALS). This study aimed to investigate the impact of FUS (R521H and P525L) on transcriptome induced pluripotent stem cells (iPSCs) iPSC-derived motor neurons (iMNs). Using RNA sequencing (RNA Seq), we characterized differentially expressed genes (DEGs), lncRNAs (DELs), subsequently predicted lncRNA-mRNA target pairs (TAR pairs). Our results show that significantly altered expression profiles mRNAs...
SUMMARY DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with metabolic processes such as replication, transcription and recombination. SPRTN is a replication-coupled DNA-dependent metalloprotease cleaves proteins crosslinked to promote DPC repair. function tightly regulated by monoubiquitin switch controls chromatin accessibility during The deubiquitinase regulating in repair unknown. Here, we identify USP11 deubiquitinase. interacts monoubiquitinated cells vitro....
An assembly of multiprotein complexes achieves chromosomal DNA replication at the fork. In eukaryotes, proliferating cell nuclear antigen (PCNA) plays a vital role in fork and is essential for viability. PCNA from several organisms, including Saccharomyces cerevisiae, has been structurally characterised. However, structural analyses fungal pathogens are limited. Recently, we have reported that opportunistic pathogen Candida albicans complements functions ScPCNA S. cerevisiae. Still, it only...