A5031698848- DNA Repair Mechanisms
- Renal Transplantation Outcomes and Treatments
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Organ Transplantation Techniques and Outcomes
- Epigenetics and DNA Methylation
- Renal Diseases and Glomerulopathies
- Protein Degradation and Inhibitors
- Bacteriophages and microbial interactions
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Genomics and Phylogenetic Studies
- Chronic Kidney Disease and Diabetes
- Prostate Cancer Treatment and Research
- CRISPR and Genetic Engineering
- Organ Donation and Transplantation
- Carcinogens and Genotoxicity Assessment
- Cancer, Lipids, and Metabolism
- HER2/EGFR in Cancer Research
- Polyomavirus and related diseases
- Prostate Cancer Diagnosis and Treatment
- Nutrition and Health in Aging
- Enzyme Production and Characterization
Mayo Clinic
2009-2025
National Cancer Institute
2022-2025
Center for Cancer Research
2022-2025
Mayo Clinic in Arizona
2012-2024
Mayo Clinic in Florida
2024
WinnMed
2012-2024
Osaka Metropolitan University
2023-2024
Tokyo Metropolitan University
2023-2024
Osaka Prefecture University
2024
Osaka City University
2006-2023
The deubiquitinating enzyme BRCA1-associated protein 1 (BAP1) possesses growth inhibitory activity and functions as a tumor suppressor. In this study we report that BAP1 also plays positive roles in cell proliferation. depletion by RNAi inhibits proliferation does overexpression of dominant negative mutant BAP1. Mass spectrometry analyses copurified proteins revealed is associated with factors involved chromatin modulation transcriptional regulation. We show the interaction host factor-1...
Emi1 (early mitotic inhibitor) inhibits APC/C (anaphase-promoting complex/cyclosome) activity during S and G2 phases, is believed to be required for proper entry. We report that plays an essential function in cell proliferation by preventing rereplication. Rereplication seen after depletion due premature activation of results destabilization geminin cyclin A, two proteins shown here play redundant roles rereplication mammalian cells. Geminin known inhibit the replication initiation factor...
Germline mutations in SPRTN cause Ruijs–Aalfs syndrome (RJALS), a disorder characterized by genome instability, progeria and early onset hepatocellular carcinoma. Spartan, the protein encoded SPRTN, is nuclear metalloprotease that involved repair of DNA–protein crosslinks (DPCs). Although Sprtn hypomorphic mice recapitulate key progeroid phenotypes RJALS, whether this model expressing low amounts Spartan prone to DPC defects spontaneous tumors unknown. Here, we showed livers accumulate DPCs...
Abstract Spartan (also known as DVC1 and C1orf124) is a PCNA-interacting protein implicated in translesion synthesis, DNA damage tolerance process that allows the replication machinery to replicate past nucleotide lesions. However, physiological relevance of has not been established. Here we report insufficiency mice causes chromosomal instability, cellular senescence early onset age-related phenotypes. Whereas complete loss embryonic lethality, hypomorphic with low amounts are viable. These...
Abstract Persistent protein obstacles on genomic DNA, such as DNA-protein crosslinks (DPCs) and tight nucleoprotein complexes, can block replication forks. DPCs be removed by the proteolytic activities of metalloprotease SPRTN or proteasome in a replication-coupled manner; however, additional mechanisms may exist to cope with diversity obstacles. Here, we show that FAM111A, PCNA-interacting protein, plays an important role mitigating effect This function FAM111A requires intact trypsin-like...
The oncoprotein transcription factor MYC is a major driver of malignancy and highly validated but challenging target for the development anticancer therapies. Novel strategies to inhibit may come from understanding co-factors it uses drive pro-tumorigenic gene expression programs, providing their role in activity understood. Here we interrogate how one co-factor, host cell (HCF)–1, contributes human Burkitt lymphoma setting. We identify genes connected mitochondrial function ribosome...
Using SDS/polyacrylamide gels that contained myelin basic protein, we identified a 46-kDa protein kinase in tobacco is transiently activated by cutting. Although the activity of was rarely detectable mature leaves, marked became apparent within several minutes after isolation leaf discs and subsided 30 min. In presence cycloheximide (CHX), did not diminish over course 2 hr, suggesting synthesis required for activation kinase. A second cutting between min 60 failed to activate kinase, whereas...
We have isolated a cDNA (cNPK1) that encodes predicted protein kinase of 690 amino acids from suspension cultures tobacco cells. The deduced sequence is closely related to those the kinases encoded by STE11 and BCK1 genes Saccharomyces cerevisiae byr2 gene Schizosaccharomyces pombe. Byr2 function in yeast mating pheromone response pathways, acts downstream C homolog PKC1 gene, which essential for normal growth division Overexpression cells truncated form cNPK1, only putative catalytic...
BRCA1-associated protein 1 (BAP1), which is frequently mutated in cancer, functions as a deubiquitinase (DUB) for histone H2A. Although BAP1 interacts with transcriptional regulator, HCF-1, and transcription factors FoxK1 FoxK2, how controls gene expression remains unclear. This study investigates the importance of DUB activity interactions FoxK2 HCF-1 regulation target genes. We show that recruits to genes through forkhead-associated domain, Thr(P)-493 on BAP1. BAP1, turn, thereby forming...
Abstract FAM111A, a serine protease, plays roles in DNA replication and antiviral defense. Missense mutations the catalytic domain cause hyper-autocleavage are associated with genetic disorders developmental defects. Despite enzyme’s biological significance, molecular architecture of FAM111A protease (SPD) is unknown. Here, we show that dimerization-dependent containing narrow, recessed active site cleaves substrates chymotrypsin-like specificity. X-ray crystal structures mutagenesis studies...
The Fanconi anemia (FA) nuclear core complex and the E2 ubiquitin-conjugating enzyme UBE2T are required for S phase DNA damage-restricted monoubiquitination of FANCD2. This constitutes a key step in FA tumor suppressor pathway, much attention has been focused on regulation at this point. Here, we address importance assembly subcellular localization FANCD2 monoubiquitination. We establish three points. First, stable can be dissociated its ability to function as an E3 ubiquitin ligase. Second,...
Uninterrupted replication across damaged DNA is critical to prevent fork collapse and resulting double-strand breaks. Rad18-mediated PCNA ubiquitination a crucial event that triggers number of downstream pathways important for lesion bypass. Here, we report characterization Spartan, an evolutionarily conserved protein containing PCNA-interacting peptide motif, called PIP box, UBZ4 ubiquitin-binding domain. Spartan nuclear forms damage-induced foci colocalize with markers stalled replication....
Translesion synthesis (TLS) employs low fidelity polymerases to replicate past damaged DNA in a potentially error-prone process.Regulatory mechanisms that prevent TLS-associated mutagenesis are unknown; however, our recent studies suggest the PCNA-binding protein Spartan plays role suppression of damage-induced mutagenesis.Here, we show negatively regulates TLS is dependent on POLD3, accessory subunit replicative polymerase Pol d.We demonstrate putative zinc metalloprotease domain SprT...
The origin recognition complex (ORC) is involved in formation of prereplicative complexes (pre-RCs) on replication origins the G1 phase. At G1/S transition, elevated cyclin E-CDK2 activity triggers 1DNA to enter S CDK cycle works as an engine that drives progression cell events by successive activation different types cyclin-CDK. However, how coordinated with initiation remains elusive. Here we report acute depletion ORC2 RNA interference (RNAi) arrests cells low activity. This result...
ABSTRACT The type-specific capsular polysaccharide (CP) of a group B streptococcus, Streptococcus agalactiae type Ia, is high-molecular-weight polymer consisting the pentasaccharide repeating unit 4)-[α- d -Neu p NAc-(2→3)-β- -Gal -(1→4)-β- -Glc NAc-(1→3)]-β- -(1. Here, cloning, sequencing, and transcription Ia-specific synthesis ( cps ) genes functional analysis these gene products are described. A 26-kb DNA fragment containing 18 complete open reading frames (ORFs) was cloned. These ORFs...