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Biology subjects

Yamashita, Y. M.

Publications and source records attributed to Yamashita, Y. M..

4 recordsLinked to original sources

A conserved function for pericentromeric satellite DNA

A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi AT-hook satellite DNA binding proteins, D. melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into chromocenters, a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding off of interphase nucleus and cell death. We propose that chromocenter and satellite DNA serves a fundamental role to achieve the universal characteristic of eukaryotic cells: full complement of the genome within a single nucleus.

cell biology

Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division

Asymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Domes role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.

cell biology

Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells

rDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in the Drosophila male germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in animals that inherit reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.

developmental biology

Germ cell connectivity enhances cell death in response to DNA damage in Drosophila testis

Two broadly known characteristics of germ cells in many organisms are their development as a cyst of interconnected cells and their high sensitivity to DNA damage. Here we provide evidence that these characteristics are linked, and that interconnectivity is a mechanism that confers to the Drosophila testis a high sensitivity to DNA damage. We show that all germ cells within a cyst die simultaneously even when only a subset of them exhibit detectable DNA damage. Compromising connectivity results in cysts in which only a subset of germ cells die upon DNA damage, lowering overall germ cell death. Our data indicate that a death-promoting signal is shared through the intercellular connections of germ cells. Taken together, we propose that intercellular connectivity is a mechanism that uniquely increases the sensitivity of the germline to DNA damage, thereby protecting the integrity of gamete genomes that are passed on to the next generation.

developmental biology