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Articles 1 - 5 of 5

Full-Text Articles in Molecular Biology

Loss Of The Cone-Enriched Caspase-7 Does Not Affect Secondary Cone Death In Retinitis Pigmentosa, Aditya Venkatesh, Shun-Yun Cheng, Claudio Punzo Dec 2017

Loss Of The Cone-Enriched Caspase-7 Does Not Affect Secondary Cone Death In Retinitis Pigmentosa, Aditya Venkatesh, Shun-Yun Cheng, Claudio Punzo

University of Massachusetts Medical School Faculty Publications

Purpose: The apoptotic mechanisms responsible for secondary cone death in retinitis pigmentosa (RP) remain largely unknown. The cone-enriched apoptotic protease caspase-7 (Casp7) is thought to be triggered by endoplasmic reticulum (ER) stress and plays a pivotal role in mice deficient in the cone cyclic nucleotide-gated channels, a deficiency that causes achromatopsia in humans and in mice with autosomal dominant rhodopsin mutations, in particular the T17M mutation. Thus, we tested in two mouse models of RP whether the cone-enriched Casp7 plays a role during secondary cone death.

Methods: Casp7 knockout mice were crossed to two different RP mouse models with significantly ...


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

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

University of Massachusetts Medical School Faculty 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 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 ...


Ki-67 Contributes To Normal Cell Cycle Progression And Inactive X Heterochromatin In P21 Checkpoint-Proficient Human Cells, Xiaoming Sun, Aizhan Bizhanova, Timothy D. Matheson, Jun Yu, Lihua Julie Zhu, Paul D. Kaufman May 2017

Ki-67 Contributes To Normal Cell Cycle Progression And Inactive X Heterochromatin In P21 Checkpoint-Proficient Human Cells, Xiaoming Sun, Aizhan Bizhanova, Timothy D. Matheson, Jun Yu, Lihua Julie Zhu, Paul D. Kaufman

University of Massachusetts Medical School Faculty Publications

Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a ...


Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer Apr 2017

Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 A. This structure not only visualizes the active ...


The 4d Nucleome Project, Job Dekker, Andrew S. Belmont, Mitchell Guttman, Victor O. Leshyk, John T. Lis, Stavros Lomvardas, Leonid A. Mirny, Clodagh C. O'Shea, Peter J. Park, Bing Ren, Joan C. Ritland Politz, Jay Shendure, Sheng Zong Jan 2017

The 4d Nucleome Project, Job Dekker, Andrew S. Belmont, Mitchell Guttman, Victor O. Leshyk, John T. Lis, Stavros Lomvardas, Leonid A. Mirny, Clodagh C. O'Shea, Peter J. Park, Bing Ren, Joan C. Ritland Politz, Jay Shendure, Sheng Zong

University of Massachusetts Medical School Faculty Publications

The spatial organization of the genome and its dynamics contribute to gene expression and cellular function in normal development as well as in disease. Although we are increasingly well equipped to determine a genome's sequence and linear chromatin composition, studying the three-dimensional organization of the genome with high spatial and temporal resolution remains challenging. The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the long term goal of gaining deeper mechanistic understanding of how the nucleus is organized. The project will ...