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University of Massachusetts Medical School

Cellular and Molecular Physiology

Chromosomes

Articles 1 - 6 of 6

Full-Text Articles in Life Sciences

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O'Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres Dec 2017

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O'Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres

University of Massachusetts Medical School Faculty Publications

Aneuploidy disrupts cellular homeostasis. However, the molecular mechanisms underlying the physiological responses and adaptation to aneuploidy are not well understood. Deciphering these mechanisms is important because aneuploidy is associated with diseases, including intellectual disability and cancer. Although tumors and mammalian aneuploid cells, including several cancer cell lines, show altered levels of sphingolipids, the role of sphingolipids in aneuploidy remains unknown. Here, we show that ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy. Sphingolipid levels are tightly linked to serine synthesis, and inhibiting either serine or sphingolipid synthesis can specifically impair the fitness ...


Crispr-Based Dna Imaging In Living Cells Reveals Cell Cycle-Dependent Chromosome Dynamics, Hanhui Ma, Li-Chun Tu, University Of Central Florida, Yu-Chieh Chung, David Grünwald, Shaojie Zhang, Thoru Pederson Sep 2017

Crispr-Based Dna Imaging In Living Cells Reveals Cell Cycle-Dependent Chromosome Dynamics, Hanhui Ma, Li-Chun Tu, University Of Central Florida, Yu-Chieh Chung, David Grünwald, Shaojie Zhang, Thoru Pederson

University of Massachusetts Medical School Faculty Publications

In contrast to the well-studied condensation and folding of chromosomes during mitosis, their dynamics in interphase are less understood. We developed a sensitive, multicolor system, CRISPR-Sirius, allowing the real-time tracking of the dynamics of chromosomal loci. We tracked loci kilobases to megabases apart and found significant variation in the inter-locus distances of each pair, indicating differing degrees of DNA contortion. We resolved two distinct modes of dynamics of loci: saltatory local movements as well as translational movements of the domain. The magnitude of both of these modes of movements increased from early to late G1, whereas the translational movements were ...


A Synthetic Biology Approach To Probing Nucleosome Symmetry, Yuichi Ichikawa, Caitlin M. Connolly, Hsin-Jung Chou, Yuanyuan Chen, Upasna Sharma, Hsuiyi V. Chen, Vineeta Bajaj, Daniel Na. Bolon, Oliver J. Rando, Paul D. Kaufman Sep 2017

A Synthetic Biology Approach To Probing Nucleosome Symmetry, Yuichi Ichikawa, Caitlin M. Connolly, Hsin-Jung Chou, Yuanyuan Chen, Upasna Sharma, Hsuiyi V. Chen, Vineeta Bajaj, Daniel Na. Bolon, Oliver J. Rando, Paul D. Kaufman

UMass Metabolic Network Publications

The repeating subunit of chromatin, the nucleosome, includes two copies of each of the four core histones, and several recent studies have reported that asymmetrically-modified nucleosomes occur at regulatory elements in vivo. To probe the mechanisms by which histone modifications are read out, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, which we extensively validated genetically and biochemically. Comparing the effects of asymmetric histone tail point mutants with those of symmetric double mutants revealed that a single methylated H3K36 per nucleosome was sufficient to silence cryptic transcription in vivo. We also demonstrate the utility of this ...


Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster Aug 2017

Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster

GSBS Dissertations and Theses

Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends ...


Xist And Cot-1 Repeat Rnas Are Integral Components Of A Complex Nuclear Scaffold Required To Maintain Saf-A And Modify Chromosome Architecture: A Dissertation, Heather J. Kolpa Apr 2016

Xist And Cot-1 Repeat Rnas Are Integral Components Of A Complex Nuclear Scaffold Required To Maintain Saf-A And Modify Chromosome Architecture: A Dissertation, Heather J. Kolpa

GSBS Dissertations and Theses

XIST RNA established the precedent for a noncoding RNA that stably associates with and regulates chromatin, however it remains poorly understood how such RNAs structurally associate with the interphase chromosome territory. I demonstrate that transgenic XIST RNA localizes in cis to an autosome as it does to the inactive X chromosome, hence the RNA recognizes a structure common to all chromosomes. I reassess the prevalent thinking in the field that a single protein, Scaffold Attachment Factor-A (SAF-A/hnRNP U), provides a single molecule bridge required to directly tether the RNA to DNA. In an extensive series of experiments in multiple ...


No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon Mar 2016

No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon

UMass Metabolic Network Publications

Previous studies of laboratory strains of budding yeast had shown that when gene copy number is altered experimentally, RNA levels generally scale accordingly. This is true when the copy number of individual genes or entire chromosomes is altered. In a recent study, Hose et al. (2015) reported that this tight correlation between gene copy number and RNA levels is not observed in recently isolated wild Saccharomyces cerevisiae variants. To understand the origins of this proposed difference in gene expression regulation between natural variants and laboratory strains of S. cerevisiae, we evaluated the karyotype and gene expression studies performed by Hose ...