Biology subjects

Wang, T.-F.

Publications and source records attributed to Wang, T.-F..

6 recordsLinked to original sources

bioRxiv2025

Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis

Rad51 and meiosis-specific Dmc1 catalyze homologous recombination (HR) between maternal and paternal chromosomes during meiosis in many sexual eukaryotes, generating three interhomolog (IH) recombination products: noncrossovers (NCOs), class I crossovers (COs), and class II COs. Some COs form chiasmata, which physically connect homologous chromosomes and ensure proper chromosome segregation during meiosis I. Meiosis is highly relevant to speciation, with the mismatch repair (MMR) system believed to prevent IH-HR, leading to postzygotic isolation between closely related species. We report that several Saccharomyces cerevisiae HR proteins exhibit anti-MMR activities, including Rad51, Rad54, and synapsis-promoting ZMM proteins (Mer3, Zip1, Zip4, and Msh4) in SK1/S288c hybrid zygotes. Srs2 (an ortholog of Escherichia coli helicase UvrD) facilitates MMR by dissembling Rad51-ssDNA presynaptic filaments. Rad51 antagonizes MMR and Srs2 to catalyze D-loop formation. Rad54s anti-MMR activity acts after Srs2 and outcompetes its pro-HR function to promote Rad51-mediated IH-HR in hybrid zygotes. Dmc1 does not possess anti-MMR activity, but exhibits better mismatch tolerability than Rad51. Following D-loop formation mediated by Dmc1 and/or Rad51, ZMM proteins promote class I IH-CO formation while limiting MMR to promote NCO formation by Sgs1 (an ortholog of E. coli RecQ helicase) and prevent class II IH-CO formation by the Mms4*Mus81 endonuclease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/636946v2_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@db6794org.highwire.dtl.DTLVardef@6d5947org.highwire.dtl.DTLVardef@1004489org.highwire.dtl.DTLVardef@938403_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMMR and HR antagonize each other in intraspecies hybrid zygotes. C_LIO_LIThe HR proteins Rad51, Rad54, and ZMM exhibit anti-MMR activities. C_LIO_LIMMR overrides HR in hybrid zygotes with anti-MMR mutations, causing hybrid sterility. C_LI

genetics↗

bioRxiv2025

Sex-biased zinc responses modulate ribosome biogenesis, protein synthesis and social defects in Cttnbp2 mutant mice

Autism spectrum disorders (ASD) are neurodevelopmental conditions influenced by genetic mutations, dietary factors, and sex-specific mechanisms, yet the interplay of these factors remains elusive. Here, we investigate the sex-biased responses of mutant mice carrying an ASD-associated mutation in Cttnbp2 to dietary zinc supplementation using behavioral assays, proteomic and bioinformatic analyses, and puromycin pulse labeling to assess protein synthesis. Our results demonstrate that zinc supplementation enhances ribosome biogenesis and increases the density and size of dendritic spines in male Cttnbp2 mutant mice, alleviating male-biased social deficits. Analyses of neuronal cultures further revealed that neurons, not astrocytes, respond to zinc to enhance protein synthesis. In contrast, female Cttnbp2 mutants exhibit resilience to differential zinc intake, even under zinc deprivation. Elevated mTOR phosphorylation and increased protein levels of translational initiation factors in female brains may provide a protective mechanism, reducing their sensitivity to zinc deficiency. Cttnbp2 mutations heighten male vulnerability to zinc deprivation, impairing social behaviors. These findings highlight zinc-regulated ribosome biogenesis and protein synthesis as critical mediators of sex-specific ASD phenotypes, offering new insights into dietary interventions.

neuroscience↗

bioRxiv2024

Ki67 regulates nuclear lipid accumulation at the chromosomal periphery to facilitate chromosome individualization during mitosis

Nuclear lipids play roles in regulatory processes such as signaling, transcriptional regulation, and DNA repair. In this report, we demonstrate that nuclear lipids may contribute to Ki-67-regulated chromosome integrity during mitosis. In COS-7 cells, nuclear lipids are enriched at the perichromosomal layer and excluded from intrachromosomal regions during early mitosis, but are then detected in intrachromosomal regions during late mitosis, as revealed by TT-ExM, an improved expansion microscopy technique that enables high-sensitivity, super-resolution imaging of proteins, lipids, and nuclear DNA. The nuclear non-histone protein Ki-67 acts as a surfactant to form a repulsive molecular brush around fully condensed sister chromatids in early mitosis, preventing the diffusion or penetration of nuclear lipids into intrachromosomal regions. Ki-67 is phosphorylated during mitosis by cyclin-dependent kinase 1 (CDK1), the best-known master regulator of the cell cycle. Both Ki-67 knockdown and reduced Ki-67 phosphorylation by CDK1 inhibitors allow nuclear lipids to penetrate chromosomal regions. Thus, both Ki-67 protein level and phosphorylation status during mitosis appear to influence the perichromosomal distribution of nuclear lipids. Ki-67 knockdown and CDK1 inhibition also lead to uneven chromosome disjunction between daughter cells, highlighting the critical role of this regulatory mechanism in ensuring accurate chromosome segregation. Given that Ki-67 has been proposed to promote chromosome individualization during open mitosis in vertebrates, our results reveal that nuclear lipid enrichment at the perichromosomal layer enhances Ki-67s ability to form a protective chromosomal envelope, which is critical for correct chromosome segregation and maintenance of genome integrity during mitosis.

cell biology↗

bioRxiv2020

Intrinsic disorder codes for leaps of protein expression

Serine(S)/threonine(T)-glutamine(Q) cluster domains (SCDs), polyglutamine (polyQ) tracts and polyglutamine/asparagine (polyQ/N) tracts are Q-rich motifs found in many proteins. SCDs often are intrinsically disordered regions that mediate protein phosphorylation and protein-protein interactions. PolyQ and polyQ/N tracts are structurally flexible sequences that trigger protein aggregation. We report that due to their high percentages of STQ or STQN amino acid content, four SCDs and three prion-causing Q/N-rich motifs of yeast proteins possess autonomous protein expression-enhancing activities. Since these Q-rich motifs can endow proteins with structural and functional plasticity, we suggest that they represent useful toolkits for evolutionary novelty. Comparative Gene Ontology (GO) analyses of the near-complete proteomes of 27 representative model eukaryotes reveal that Q-rich motifs prevail in proteins involved in specialized biological processes, including Saccharomyces cerevisiae RNA-mediated transposition and pseudohyphal growth, Candida albicans filamentous growth, ciliate peptidyl-glutamic acid modification and microtubule-based movement, Tetrahymena thermophila xylan catabolism and meiosis, Dictyostelium discoideum development and sexual cycles, Plasmodium falciparum infection, and the nervous systems of Drosophila melanogaster, Mus musculus and Homo sapiens. We also show that Q-rich-motif proteins are expanded massively in ten ciliates with reassigned TAAQ and TAGQ codons. Notably, the usage frequency of CAGQ is much lower in ciliates with reassigned TAAQ and TAGQ codons than in organisms with expanded and unstable Q runs (e.g., D. melanogaster and H. sapiens), indicating that the use of noncanonical stop codons in ciliates may have coevolved with codon usage biases to avoid triplet repeat disorders mediated by CAG/GTC replication slippage.

biochemistry↗

bioRxiv2019

Two different pathways for initiation of Trichoderma reesei Rad51-only meiotic recombination

BackgroundMeiotic recombination is mainly, but not exclusively, initiated by Spo11-induced double strand breaks (DSBs) in some sexual eukaryotes. DSBs are repaired by one or two RecA-like recombinases (ubiquitous Rad51 and meiosis-specific Dmc1). In yeast and mammals, Dmc1 is superior to Rad51 in tolerating mismatched sequences during highly polymorphic hybrid meiosis. The mechanisms underlying Rad51-only meiotic recombination remain less studied.\n\nResultsThe Rad51-only filamentous fungus Trichoderma reesei has only one spo11 gene. Removal of spo11 from T. reesei genome does not affect normal sexual development, meiosis or chromosome synapsis, but results in decrease of interhomolog recombination products to 70%, crossover homeostasis and lower genetic interference. Our results also suggest that T. reesei Rad51, like yeast and mammalian Dmc1 (but not Rad51), can tolerate mismatched sequences during meiotic recombination. Moreover, Topoisomerase II might act redundantly (and predominantly) with Spo11 to initiate meiotic recombination.\n\nConclusionWe suggest that T. reesei is an emerging model for studying Spo11-independent and Rad51-only meiosis.

genetics↗

bioRxiv2017

Trichoderma reesei Complete Genome Sequence, Repeat-Induced Point Mutation And Partitioning Of CAZyme Gene Clusters

Trichoderma reesei (Ascomycota, Pezizomycotina) QM6a is a model fungus for a broad spectrum of physiological phenomena, including plant cell wall degradation, industrial production of enzymes, light responses, conidiation, sexual development, polyketide biosynthesis and plant-fungal interactions. The genomes of QM6a and its high-enzyme producing mutants have been sequenced by second-generation-sequencing methods and are publicly available from the Joint Genome Institute (JGI). While these genome sequences have offered useful information for genomic and transcriptomic studies, their limitations and especially their short read lengths make them poorly suited for some particular biological problems, including assembly, genome-wide determination of chromosome architecture and genetic modification or engineering. We integrated Pacific Biosciences and Illumina sequencing platforms for the highest-quality genome assembly yet achieved, revealing seven telomere-to-telomere chromosomes (34,922,528 bp; 10877 genes) with 1630 newly-predicted genes and >1.5 Mb of new sequences. Most new sequences are located on AT-rich blocks, including 7 centromeres, 14 subtelomeres and 2329 interspersed AT-rich blocks. The seven QM6a centromeres separately consist of 24 conserved repeats and 37 putative centromere-encoded genes. These findings open up a new perspective for future centromere and chromosome architecture studies. Next, we demonstrate that sexual crossing readily induced cytosine-to-thymine point mutations on both tandem and unlinked duplicated sequences. We also show by bioinformatic analysis that Trichoderma reesei has evolved a robust repeat-induced point mutation (RIP) system to accumulate AT-rich sequences, with longer AT-rich blocks having more RIP mutations. The widespread distribution of AT-rich blocks correlates genome-wide partitions with gene clusters, explaining why clustering of genes has been reported to not influence gene expression in Trichoderma reesei. Compartmentation of ancestral gene clusters by AT-rich blocks might promote flexibilities that are evolutionarily advantageous in this fungus soil habitats and other natural environments. Our analyses, together with the complete genome sequence, provide a better blueprint for biotechnological and industrial applications.

genomics↗