A5064310333- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Heat shock proteins research
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Kruppel-like factors research
- Chromosomal and Genetic Variations
- Herpesvirus Infections and Treatments
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Cancer Cells and Metastasis
- Nutrition, Genetics, and Disease
- Cytomegalovirus and herpesvirus research
- Nuclear Structure and Function
- RNA Research and Splicing
- ATP Synthase and ATPases Research
- Fungal and yeast genetics research
Yangtze University
2025
National Taiwan University
2013-2023
Academia Sinica
2017
National Taiwan University Hospital
2005-2014
Czech Academy of Sciences, Institute of Microbiology
2012
Rutgers, The State University of New Jersey
1995-2009
Princeton University
1998-2002
Massachusetts General Hospital
1994
ManySaccharomyces telomeres bear one or more copies of the repetitive Y element followed by ϳ350 bp telomerase-generated C 1-3 A/TG repeats.Although most cells lacking a gene required for telomerase pathway die after 50 to 100 cell divisions, survivors arise spontaneously in such cultures.These have two distinct patterns telomeric DNA (V.Lundblad and E. H. Blackburn, Cell 73:347-360, 1993).The common patterns, seen type I survivors, is tandem amplification very short tracts DNA.By...
In Saccharomyces cerevisiae, the telomerase components Est2p, TLC1 RNA, Est1p, and Est3p are thought to form a complex that acts late during chromosome replication (S phase) upon recruitment by Cdc13p, telomeric DNA binding protein. Consistent with this model, we show Cdc13p telomere-associated at time. However, but not also binds telomeres before S phase. The cdc13-2 allele has been proposed be defective in recruitment, yet Est1p Est2p telomere association persists cells. These findings...
Mutations in the yeast Saccharomyces cerevisiae PIF1 gene, which encodes a 5'-to-3' DNA helicase, cause telomere lengthening and large increase formation rate of new telomeres. Here, we show that Pif1p acts by inhibiting telomerase rather than telomere-telomere recombination, this inhibition requires helicase activity Pif1p. Overexpression enzymatically active causes shortening. Thus, is catalytic inhibitor telomerase-mediated lengthening. Because associated with telomeric vivo, its effects...
Abstract Background Hypoxia induces the epithelial-mesenchymal transition, EMT, to promote cancer metastasis. In addition transcriptional regulation mediated by hypoxia-inducible factors, HIFs, other epigenetic mechanisms of gene regulation, such as histone modifications and DNA methylation, are utilized under hypoxia. However, whether demethylation TET1, a dioxygenase converting 5-methylcytosine, 5mC, into 5-hydroxymethylcytosine, 5hmC, plays role in hypoxia-induced EMT is largely unknown....
The BGLF4 protein kinase of Epstein-Barr virus (EBV) is a member the conserved family herpesvirus kinases which, to some extent, have function similar that cellular cyclin-dependent in regulating multiple and viral substrates. In yeast two-hybrid screening assay, splicing variant interferon (IFN) regulatory factor 3 (IRF3) was found interact with protein. This interaction defined further by coimmunoprecipitation transfected cells glutathione S-transferase (GST) pull-down vitro. Using...
The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters most of their vivo targets. Budding yeast Cdc13p contains two motifs, suggesting it might be a target Mec1p/Tel1p (yeast ATR/ATM). Here we demonstrated the telomerase recruitment domain is phosphorylated by Mec1p Tel1p. Gel analysis showed Mec1/Tel1-dependent post-translational modification. Using an immunoprecipitate (IP)-kinase assay, phosphorylates on serine 225, 249, 255 306, Tel1p 249...
Heat shock protein 60 (HSP60) plays an essential role in assisting many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed different types of human cancers with metastasis (e.g. pancreatic cancer and large bowel carcinoma). However, the remains little known. Aberrant activation β-catenin a key tumorigenesis metastasis. Here, we show that overexpression induces metastatic phenotypes vitro vivo . interacts β-catenin, increases levels through apical...
Nijmegen breakage syndrome (NBS) is a chromosomal-instability associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product, NBS1, component of the MRE11-RAD50-NBS1 (MRN) complex, central player double strand break (DSB) repair. In response to radiation, NBS1 phosphorylated by ATM, MRN complex relocalizes form punctate nuclear foci for DNA controls both localization complexes radiation-induced focus formation. We report here that KPNA2...
Abstract Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most frequent type of cancer worldwide. However, molecular genetic alterations underlying its malignant behavior progression are little known. We showed previously that c-MYC directly activates expression DNA double-strand break repair gene NBS1, NBS1 overexpression contributes to transformation. Here, we investigate role in HNSCC. Experimental Design: Immunohistochemistry analysis was done 81 locally...
The zinc finger Krüppel-like transcription factor 4 (KLF4) has been implicated in cancer formation and stem cell regulation. However, the function of KLF4 tumorigenesis regulation are poorly understood due to limited knowledge its targets these cells. In this study, we have revealed a surprising link between telomerase that offers important insight into how contributes sufficiently activated expression human catalytic subunit, reverse transcriptase (hTERT), telomerase-low alternative...
Abstract SMYD3 methyltransferase is nearly undetectable in normal human tissues but highly expressed several cancers, including breast cancer, although its contributions to pathogenesis this setting are unclear. Here we report that histone H2A.Z.1 a substrate of supports malignancy. SMYD3-mediated dimethylation at lysine 101 (H2A.Z.1K101me2) increased stability by preventing binding the removal chaperone ANP32E and facilitating interaction with H3. Moreover, microarray analysis identified...
Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) implicated controlling genome integrity, formation stemness. Previous studies identified that Krüppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression contributes to the maintenance of self-renewal ESCs. However, little known about how KLF4 regulates TERT expression. Here, we discover poly(ADP-ribose) polymerase 1 (PARP1) as a novel KLF4-interacting partner. Knockdown PARP1...
Introduction Branches are important for soybean yield, and previous studies examining branch traits have primarily focused on number (BN), while research assessing internode (BIN), length (BL), (BIL) remains insufficient. Methods A recombinant inbred line (RIL) population consisting of 364 lines was constructed by crossing ZD41 ZYD02878. Based the RIL population, we genetically analyzed four using different GWAS methods including efficient mixed-model association expedited, restricted...
The mammalian brain relies primarily on glucose for its energy needs. Delivery of this nutrient to the is mediated by transporter-1 (Glut1) protein. Low Glut1 thwarts entry into brain, causing an crisis and, triggering, in one instance, debilitating neurodevelopmental condition, deficiency syndrome (Glut1DS). Current treatments Glut1DS are sub-optimal, as none address root cause, low Glut1, condition. Levels transporter must respond rapidly brain's changing requirements. This necessitates...
The c-myc proto-oncogene encodes a ubiquitous transcription factor involved in the control of cell growth and implicated inducing tumorigenesis. Understanding function c-Myc its role cancer depends upon identification target genes. Nijmegen breakage syndrome (NBS) is chromosomal-instability associated with predisposition, radiosensitivity, chromosomal instability. NBS gene product, NBS1 (p95 or nibrin), part hMre11 complex, central player double-strand break (DSB) repair. contains domains...
Transcription and replication of the influenza A virus RNA genome occur in nucleus through viral RNA-dependent polymerase consisting PB1, PB2, PA. Cellular factors that associate with complex play important roles these processes. To look for cellular could PA protein, we have carried out a yeast two-hybrid screen using HeLa cell cDNA library. We identified six proteins may interact focused our study on one new PA-interacting proteins, HAX1, protein antiapoptotic function. By glutathione...
Abstract Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation. Yeast Cip1 is a Cdk1 and Cln2-associated protein. However, the function regulation of are still poorly understood. Here we report that expression co-regulated by cell-cycle-mediated factor Mcm1 stress-mediated factors Msn2/4. Overexpression arrests through inhibition Cdk1–G1 cyclin complexes at G1 stage stress-activated protein kinase-dependent T65, T69, T73 phosphorylation may...