Although nonrandom sister chromatid segregation is a singular property of distributed stem cells (DSCs) that are responsible for renewing and repairing mature vertebrate tissues, both its cellular function and its molecular mechanism remain unknown. This situation persists in part because of the lack of facile methods for detecting and quantifying nonrandom segregating cells and for identifying chromosomes with immortal DNA strands, the cellular molecules that signify nonrandom segregation. During nonrandom segregation, at each mitosis, asymmetrically self-renewing DSCs continuously cosegregate to themselves the set of chromosomes that contain immortal DNA strands, which are the oldest DNA strands. Here, we report the discovery of a molecular asymmetry between segregating sets of immortal chromosomes and opposed mortal chromosomes (i.e., containing the younger set of DNA template strands) that constitutes a new convenient biomarker for detection of cells undergoing nonrandom segregation and direct delineation of chromosomes that bear immortal DNA strands. In both cells engineered with DSC-specific properties and ex vivo-expanded mouse hair follicle stem cells, the histone H2A variant H2A.Z shows specific immunodetection on immortal DNA chromosomes. Cell fixation analyses indicate that H2A.Z is present on mortal chromosomes as well but is cloaked from immunodetection, and the cloaking entity is acid labile. The H2A.Z chromosomal asymmetry produced by molecular cloaking provides a first direct assay for nonrandom segregation and for chromosomes with immortal DNA strands. It also seems likely to manifest an important aspect of the underlying mechanism(s) responsible for nonrandom sister chromatid segregation in DSCs.
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Neural Netw
November 2024
Research Institute of Electrical Communication (RIEC), Tohoku University, Sendai, Japan; Graduate School of Engineering, Tohoku University, Sendai, Japan.
Hierarchically modular organization is a canonical network topology that is evolutionarily conserved in the nervous systems of animals. Within the network, neurons form directional connections defined by the growth of their axonal terminals. However, this topology is dissimilar to the network formed by dissociated neurons in culture because they form randomly connected networks on homogeneous substrates.
View Article and Find Full Text PDFBiochem Soc Trans
December 2024
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
The 2-micron plasmid residing within the host budding yeast Saccharomyces cerevisiae nucleus serves as a model system for understanding the mechanism of segregation and stable maintenance of circular endogenously present extrachromosomal DNA in eukaryotic cells. The plasmid is maintained at a high average copy number (40-60 copies per yeast cell) through generations despite there is no apparent benefit to the host. Notably, the segregation mechanism of 2-micron plasmid shares significant similarities with those of bacterial low-copy-number plasmids and episomal forms of viral genomes in mammalian cells.
View Article and Find Full Text PDFmedRxiv
November 2024
College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA, 52240.
Background: Disturbances in the intricate processes that control craniofacial morphogenesis can result in birth defects, most common of which are orofacial clefts (OFCs). Nonsyndromic cleft lip (nsCL), one of the phenotypic forms amongst OFCs, has a non-random laterality presentation with the left side being affected twice as often compared to the right side. This study investigates the etiology of nsCL and the factors contributing to its laterality using a pair of monozygotic twins with mirror-image cleft lip.
View Article and Find Full Text PDFMultiple biomolecular condensates coexist at the pre- and post- synapse to enable vesicle dynamics and controlled neurotransmitter release in the brain. In pre-synapses, intrinsically disordered regions (IDRs) of synaptic proteins are drivers of condensation that enable clustering of synaptic vesicles (SVs). Using computational analysis, we show that the IDRs of SV proteins feature evolutionarily conserved non-random compositional biases and sequence patterns.
View Article and Find Full Text PDFNat Ecol Evol
August 2024
Laboratory of Social Evolution and Behavior, The Rockefeller University, New York, NY, USA.
According to Mendel's second law, chromosomes segregate randomly in meiosis. Non-random segregation is primarily known for cases of selfish meiotic drive in females, in which particular alleles bias their own transmission into the oocyte. Here we report a rare example of unselfish meiotic drive for crossover inheritance in the clonal raider ant, Ooceraea biroi, in which both alleles are co-inherited at all loci across the entire genome.
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