A5045550226- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Fungal and yeast genetics research
- Cancer-related gene regulation
- Animal Genetics and Reproduction
- Plant Molecular Biology Research
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- Plant Gene Expression Analysis
- Advanced Battery Materials and Technologies
- Sirtuins and Resveratrol in Medicine
- Tea Polyphenols and Effects
- Wastewater Treatment and Nitrogen Removal
University of Chinese Academy of Sciences
2015-2024
Center for Excellence in Molecular Cell Science
2012-2024
Chinese Academy of Sciences
2011-2024
Center for Excellence in Molecular Plant Sciences
2024
Nantong University
2024
Augusta University
2024
University of Pennsylvania
2024
ShanghaiTech University
2015-2023
Shanghai Institutes for Biological Sciences
2005-2016
MRC Laboratory of Molecular Biology
2005-2013
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...
Recent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation. CBP p300 have been shown catalyze multiple but not conserved in evolution, raising the question as existence other enzymes for histone functional relationship between well-characterized acetylation acylation. In this study, we focus on catalyzing crotonylation demonstrate among known acetyltransferases, MOF, addition p300, also possesses...
Human MRG15 is a transcription factor that plays vital role in embryonic development, cell proliferation and cellular senescence. It comprises putative chromo domain the N-terminal part has been shown to participate chromatin remodeling regulation. We report here crystal structure of human at 2.2 Å resolution. The consists β-barrel long α-helix assumes more similar Drosophila MOF barrel than typical HP1/Pc domains. core contains hydrophobic pocket formed by three conserved aromatic residues...
Telomeres are protein–DNA structures found at the ends of linear chromosomes and crucial for genome integrity. Telomeric DNA length is primarily maintained by enzyme telomerase. Cells lacking telomerase will undergo senescence when telomeres become critically short. In Saccharomyces cerevisiae, a very small percentage cells can remain viable lengthening via two distinct homologous recombination pathways. These “survivor” classified as either Type I or II, with each class survivor possessing...
In the eukaryotic genome, transcriptionally silent chromatin tends to propagate along a chromosome and encroach upon adjacent active chromatin. The silencing machinery can be stopped by boundary elements. We performed screen in Saccharomyces cerevisiae for proteins that may contribute establishment of boundary. found disruption histone deacetylase Rpd3p results defective activity, leading Sir-dependent local propagation transcriptional repression. rpd3Δ cells, amount Sir2p was normally...
DNA polymerase δ is usually isolated as a heterodimer composed of 125 kDa catalytic subunit and 50 small unknown function. The enzyme distributive by itself requires an accessory protein, the proliferating cell nuclear antigen (PCNA), for highly processive synthesis. We have recently demonstrated that human (p125) expressed in baculovirus-infected insect cells, contrast to native heterodimeric calf thymus δ, not responsive stimulation PCNA. To determine whether lack response PCNA recombinant...
Recent studies have highlighted the histone H3K4 methylation (H3K4me)-dependent transcriptional repression in Saccharomyces cerevisiae; however, underlying mechanism remains inexplicit.Here, we report that H3K4me inhibits basal PHO5 transcription under high-phosphate conditions by suppressing nucleosome disassembly at promoter.We found derepression of promoter SET1 deletion resulted a labile chromatin structure, allowing more binding RNA polymerase II (Pol II) but not transactivators Pho2...
Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show histones dynamically acetylated on H4K12 at telomeric heterochromatin, acetylation regulates several of telomere properties. Using a de novo formation assay, surprisingly found survived heterochromatin. Consistently, histone...
Rad6 and Bre1, ubiquitin-conjugating E2 E3 enzymes respectively, are responsible for histone H2B lysine 123 mono-ubiquitination (H2Bub1) in Saccharomyces cerevisiae. Previous studies have shown that Bre1 regulate telomere length recombination. However, the underlying molecular mechanism remains largely unknown. Here we report H2BK123 mutation results shortening, while inactivation of Ubp8 and/or Ubp10, deubiquitinases H2Bub1, leads to lengthening Rad6-Bre1-dependent manner. In...
In eukaryotic organisms, genetic information is usually carried on multiple chromosomes. Whether and how the number configuration of chromosomes affect organismal fitness speciation remain unclear. Here, we have successfully established several single-chromosome fission yeast Schizosaccharomyces pombe strains, in which three natural been fused into one giant chromosome different orders. Chromosome fusions accompanied by deletions telomeres centromeres result loss chromosomal interactions a...
The end replication problem refers to the incomplete of parental DNA at telomeres, a process whose molecular depiction is hampered by complex nature telomere ends. Here we recapitulate this using synthetic de novo in yeast and delineate distinct fates ends vivo. We show that lagging strand carries ~10 nt 3-overhang, while leading has Yku-protected blunt end, which prevalent on native telomeres. In addition, RNase H2 but not H1 mainly responsible for removal last RNA primer. Consistently,...
The Saccharomyces cerevisiae Pif1p DNA helicase is the prototype member of a subfamily conserved from yeast to humans. S. has two PIF1-like genes, PIF1 itself and RRM3, that have roles in maintenance telomeric, ribosomal, mitochondrial DNA. Here we describe isolation characterization ofpfh1 + , aSchizosaccharomyces pombe gene encodes Pif1-like protein. Pfh1p was only protein with high identity Pif1p. Unlike twoS. Pif1 proteins, essential. Like SaccharomycesPif1p, truncated form had 5′ 3′...
Summary The unicellular eukaryotic organisms represent the popular model systems to understand aging in eukaryotes. Candida albicans , a polymorphic fungus, appears be another distinctive addition budding yeast Saccharomyces cerevisiae and fission Schizosaccharomyces pombe . two types of cells, (blastospore) form hyphal (filamentous) form, have similar replicative lifespan. Taking advantage morphologic changes, we are able obtain cells different ages. Old tend accumulate glycogen oxidatively...
In eukaryotes, chromosomal processes are usually modulated through chromatin-modifying complexes that dynamically targeted to specific regions of chromatin. this study, we show the chromatin-remodeling complex SWR1 (SWR1-C) uses a distinct strategy regulate heterochromatin spreading. Swr1 binds in stable manner near prepare for H2A.Z deposition, which can be triggered by NuA4-mediated acetylation histone H4. We also demonstrate experiments with Swc4, module shared NuA4 and SWR1-C, coupled...
KEOPS complex is one of the most conserved protein complexes in eukaryotes. It plays important roles both telomere uncapping and tRNA N6-threonylcarbamoyladenosine (t6A) modification budding yeast. But whether any DNA repair remains unknown. Here, we show that positive damage response homologous recombination-mediated independently its t6A synthesis function. Additionally, displays binding activity vitro, recruited to chromatin at breaks vivo, suggesting a direct role DSB repair....
The interaction between proliferating cell nuclear antigen (PCNA) and DNA polymerase δ is essential for processive synthesis during replication/repair; however, the identity of subunit that directly interacts with PCNA has not been resolved until now. In present study we have used reciprocal co-immunoprecipitation experiments to determine which two subunits core δ, 125-kDa catalytic or 50-kDa small subunit, PCNA. We found co-immunoprecipitated human p50, as well calf thymus heterodimer, but...
Rtt106p is a Saccharomyces cerevisiae histone chaperone with roles in heterochromatin silencing and nucleosome assembly. The molecular mechanism by which engages chromatin dynamics remains unclear. Here, we report the 2.5 A crystal structure of core domain Rtt106p, adopts an unusual "double pleckstrin homology" architecture that represents novel structural mode for chaperones. H3-H4-binding region double-stranded DNA-binding have been identified. Mutagenesis studies reveal DNA binding...
Recent transcription of GAL genes transiently leaves an H3K4 methylation mark at their promoters, providing epigenetic memory for the recent transcriptional activity. However, physiological significance this is enigmatic. In our study, we show that transient di- and trimethylation recently transcribed GAL1 inhibited reinduction GAL1. The functioned by recruiting Isw1 ATPase onto thereby limiting action RNA polymerase II during reactivation. Strikingly, was also observed promoters inositol-...