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https://www.readbyqxmd.com/read/29661843/functional-analysis-of-hif1-histone-chaperone-in-saccharomyces-cerevisiae
#1
Nora S Dannah, Syed Nabeel-Shah, Christoph F Kurat, Sarah A Sabatinos, Jeffrey Fillingham
The Hif1 protein in the yeast Saccharomyces cerevisie is an evolutionarily conserved H3/H4-specific chaperone and a subunit of the nuclear Hat1 complex that catalyzes the acetylation of newly synthesized histone H4. Hif1, as well as its human homolog NASP, has been implicated in an array of chromatin-related processes including histone H3/H4 transport, chromatin assembly and DNA repair. In this study, we elucidate the functional aspects of Hif1. Initially we establish the wide distribution of Hif1 homologs with an evolutionarily conserved pattern of four tetratricopeptide repeats (TPR) motifs throughout the major fungal lineages and beyond...
April 16, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29478807/the-histone-chaperones-asf1-and-caf-1-promote-mms22l-tonsl-mediated-rad51-loading-onto-ssdna-during-homologous-recombination-in-human-cells
#2
Ting-Hsiang Huang, Faith Fowler, Chin-Chuan Chen, Zih-Jie Shen, Barry Sleckman, Jessica K Tyler
The access-repair-restore model for the role of chromatin in DNA repair infers that chromatin is a mere obstacle to DNA repair. However, here we show that blocking chromatin assembly, via knockdown of the histone chaperones ASF1 or CAF-1 or a mutation that prevents ASF1A binding to histones, hinders Rad51 loading onto ssDNA during homologous recombination. This is a consequence of reduced recruitment of the Rad51 loader MMS22L-TONSL to ssDNA, resulting in persistent RPA foci, extensive DNA end resection, persistent activation of the ATR-Chk1 pathway, and cell cycle arrest...
March 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29383801/preserving-salivary-gland-physiology-against-genotoxic-damage-the-tousled-way
#3
Gulshan Sunavala-Dossabhoy
Tousled and its homologs are evolutionarily conserved serine/threonine kinases present in plants and animals. Human Tousled-like kinases, TLK1 and TLK2, are implicated in chromatin assembly during DNA replication, chromosome segregation during mitosis, as well as in DNA damage response and repair. They share a high degree of sequence similarity, but have few non-redundant functions. Our lab has studied TLK1, and found that it increases the resistance of cells to ionizing radiation (IR) damage through expedited double strand break (DSB) repair...
January 30, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29300933/structural-characterization-of-the-asf1-rtt109-interaction-and-its-role-in-histone-acetylation
#4
Lukas Lercher, Nataliya Danilenko, John Kirkpatrick, Teresa Carlomagno
Acetylation of histone H3 at lysine-56 by the histone acetyltransferase Rtt109 in lower eukaryotes is important for maintaining genomic integrity and is required for C. albicans pathogenicity. Rtt109 is activated by association with two different histone chaperones, Vps75 and Asf1, through an unknown mechanism. Here, we reveal that the Rtt109 C-terminus interacts directly with Asf1 and elucidate the structural basis of this interaction. In addition, we find that the H3 N-terminus can interact via the same interface on Asf1, leading to a competition between the two interaction partners...
March 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29247771/in-vitro-in-vivo-antioxidant-and-hepatoprotective-potential-of-defatted-extract-and-flavonoids-isolated-from-astragalus-spruneri-boiss-fabaceae
#5
Magdalena Kondeva-Burdina, Aleksandar Shkondrov, Rumyana Simeonova, Vessela Vitcheva, Ilina Krasteva, Iliana Ionkova
The aim of the current study was to evaluate the effect of a defatted extract (EAS) and three flavonoids, isolated from Astragalus spruneri Boiss. (Fabaceae) using in vitro/in vivo models of liver injury. The EAS was characterized by HPLC and flavonoids (14 mg/g dw) and saponins (8 mg/g dw) were proved. The flavonoids (ASF1, ASF3 and ASF5) were isolated from the same extract and partially identified by LC-MS. In in vitro models of non-enzyme induced (Fe2+ /AA) lipid peroxidation in isolated liver microsomes and CCl4 -induced metabolic bioactivation and t-BuOOH-induced oxidative stress in isolated rat hepatocytes, both EAS and the flavonoids exerted similar to silybin (positive control) an antioxidant and cytoprotective activity, discerned by decreased MDA production in the microsomes and by preserved cell viability and GSH levels as well as by decreased LDH activity and MDA quantity in isolated rat hepatocytes...
January 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29035199/structure-based-nuclear-import-mechanism-of-histones-h3-and-h4-mediated-by-kap123
#6
Sojin An, Jungmin Yoon, Hanseong Kim, Ji-Joon Song, Uhn-Soo Cho
Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear localization signals (NLSs) of cytoplasmic histones H3 and H4 and translocates them into the nucleus during DNA replication. Mechanistic questions include H3- and H4-NLS redundancy toward Kap123 and the role of the conserved diacetylation of cytoplasmic H4 (K5ac and K12ac) in Kap123-mediated histone nuclear translocation. Here, we report crystal structures of full-length Kluyveromyces lactis Kap123 alone and in complex with H3- and H4-NLSs...
October 16, 2017: ELife
https://www.readbyqxmd.com/read/28934510/caf-1-induced-oligomerization-of-histones-h3-h4-and-mutually-exclusive-interactions-with-asf1-guide-h3-h4-transitions-among-histone-chaperones-and-dna
#7
Wallace H Liu, Sarah C Roemer, Alex M Port, Mair E A Churchill
No abstract text is available yet for this article.
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28749957/delineation-of-the-role-of-chromatin-assembly-and-the-rtt101mms1-e3-ubiquitin-ligase-in-dna-damage-checkpoint-recovery-in-budding-yeast
#8
Li-Ting Diao, Chin-Chuan Chen, Briana Dennehey, Sangita Pal, Pingping Wang, Zie-Jie Shen, Angela Deem, Jessica K Tyler
The DNA damage checkpoint is activated in response to DNA double-strand breaks (DSBs). We had previously shown that chromatin assembly mediated by the histone chaperone Asf1 triggers inactivation of the DNA damage checkpoint in yeast after DSB repair, also called checkpoint recovery. Here we show that chromatin assembly factor 1 (CAF-1) also contributes to chromatin reassembly after DSB repair, explaining its role in checkpoint recovery. Towards understanding how chromatin assembly promotes checkpoint recovery, we find persistent presence of the damage sensors Ddc1 and Ddc2 after DSB repair in asf1 mutants...
2017: PloS One
https://www.readbyqxmd.com/read/28708136/differential-requirements-for-tousled-like-kinases-1-and-2-in-mammalian-development
#9
Sandra Segura-Bayona, Philip A Knobel, Helena González-Burón, Sameh A Youssef, Aida Peña-Blanco, Étienne Coyaud, Teresa López-Rovira, Katrin Rein, Lluís Palenzuela, Julien Colombelli, Stephen Forrow, Brian Raught, Anja Groth, Alain de Bruin, Travis H Stracker
The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type...
November 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28522692/mitotic-chromosome-assembly-despite-nucleosome-depletion-in-xenopus-egg-extracts
#10
Keishi Shintomi, Fukashi Inoue, Hiroshi Watanabe, Keita Ohsumi, Miho Ohsugi, Tatsuya Hirano
The nucleosome is the fundamental structural unit of eukaryotic chromatin. During mitosis, duplicated nucleosome fibers are organized into a pair of rod-shaped structures (chromatids) within a mitotic chromosome. However, it remains unclear whether nucleosome assembly is indeed an essential prerequisite for mitotic chromosome assembly. We combined mouse sperm nuclei and Xenopus cell-free egg extracts depleted of the histone chaperone Asf1 and found that chromatid-like structures could be assembled even in the near absence of nucleosomes...
June 23, 2017: Science
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#11
Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen, Cheng-Fu Kao
Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28381790/the-wd40-domain-of-hira-is-essential-for-ri-nucleosome-assembly-in-xenopus-egg-extracts
#12
Ruibin Zhu, Mari Iwabuchi, Keita Ohsumi
Histone chaperones are a group of histone-binding proteins that facilitate the assembly of nucleosomes, the fundamental structural units of chromatin in eukaryotes. In nucleosome assembly, deposition of a histone H3-H4 tetramer onto DNA is the first and critical step, which is mediated by the histone chaperones HIRA and CAF-1. HIRA and CAF-1 are reportedly involved in DNA replication independent (RI) and replication coupled nucleosome assembly, respectively. However, the mechanisms by which they mediate histone deposition remain unclear...
2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28320872/the-drosophila-daxx-like-protein-dlp-cooperates-with-asf1-for-h3-3-deposition-and-heterochromatin-formation
#13
Catherine Fromental-Ramain, Philippe Ramain, Ali Hamiche
Histone variants are nonallelic isoforms of canonical histones, and they are deposited, in contrast to canonical histones, in a replication-independent (RI) manner. RI deposition of H3.3, a histone variant from the H3.3 family, is mediated in mammals by distinct pathways involving either the histone regulator A (HIRA) complex or the death-associated protein (DAXX)/α-thalassemia X-linked mental retardation protein (ATRX) complex. Here, we investigated the function of the Drosophila DAXX-like protein (DLP) by using both fly genetic approaches and protein biochemistry...
June 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28123037/snasp-and-asf1a-function-through-both-competitive-and-compatible-modes-of-histone-binding
#14
Andrew Bowman, Akiko Koide, Jay S Goodman, Meaghan E Colling, Daria Zinne, Shohei Koide, Andreas G Ladurner
Histone chaperones are proteins that interact with histones to regulate the thermodynamic process of nucleosome assembly. sNASP and ASF1 are conserved histone chaperones that interact with histones H3 and H4 and are found in a multi-chaperoning complex in vivo Previously we identified a short peptide motif within H3 that binds to the TPR domain of sNASP with nanomolar affinity. Interestingly, this peptide motif is sequestered within the known ASF1-H3-H4 interface, raising the question of how these two proteins are found in complex together with histones when they share the same binding site...
January 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27753532/histone-chaperone-asf1b-promotes-human-%C3%AE-cell-proliferation-via-recruitment-of-histone-h3-3
#15
Pradyut K Paul, Mary E Rabaglia, Chen-Yu Wang, Donald S Stapleton, Ning Leng, Christina Kendziorski, Peter W Lewis, Mark P Keller, Alan D Attie
Anti-silencing function 1 (ASF1) is a histone H3-H4 chaperone involved in DNA replication and repair, and transcriptional regulation. Here, we identify ASF1B, the mammalian paralog to ASF1, as a proliferation-inducing histone chaperone in human β-cells. Overexpression of ASF1B led to distinct transcriptional signatures consistent with increased cellular proliferation and reduced cellular death. Using multiple methods of monitoring proliferation and mitotic progression, we show that overexpression of ASF1B is sufficient to induce human β-cell proliferation...
December 2016: Cell Cycle
https://www.readbyqxmd.com/read/27669733/mechanisms-underlying-acrolein-mediated-inhibition-of-chromatin-assembly
#16
Lei Fang, Danqi Chen, Clinton Yu, Hongjie Li, Jason Brocato, Lan Huang, Chunyuan Jin
Acrolein is a major component of cigarette smoke and cooking fumes. Previously, we reported that acrolein compromises chromatin assembly; however, underlying mechanisms have not been defined. Here, we report that acrolein reacts with lysine residues, including lysines 5 and 12, sites important for chromatin assembly, on histone H4 in vitro and in vivo Acrolein-modified histones are resistant to acetylation, suggesting that the reduced H4K12 acetylation that occurs following acrolein exposure is probably due to the formation of acrolein-histone lysine adducts...
December 1, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27645054/rrm3-regulates-epigenetic-conversions-in-saccharomyces-cerevisiae-in-conjunction-with-chromatin-assembly-factor-i
#17
Brandon Wyse, Roxanne Oshidari, Hollie Rowlands, Sanna Abbasi, Krassimir Yankulov
Chromatin structures are transmitted to daughter cells through a complex system of nucleosome disassembly and re-assembly at the advancing replication forks. However, the role of replication pausing in the transmission and perturbation of chromatin structures has not been addressed. RRM3 encodes a DNA helicase, which facilitates replication at sites covered with non-histone protein complexes (tRNA genes, active gene promoters, telomeres) in Saccharomyces cerevisiae. In this report we show that the deletion of RRM3 reduces the frequency of epigenetic conversions in the subtelomeric regions of the chromosomes...
July 3, 2016: Nucleus
https://www.readbyqxmd.com/read/27334407/a-polar-ring-endows-improved-specificity-to-an-antibody-fragment
#18
Zachary P Schaefer, Lucas J Bailey, Anthony A Kossiakoff
Engineering monovalent Fab fragments into bivalent formats like IgGs or F(ab')2 can lead to aggregation presumably because of nonspecific off-target interactions that induce aggregation. In an effort to further understand the molecular determinants of nonspecific interactions for engineered antibodies and natively folded proteins in general, we focused on a synthetic Fab with low nanomolar affinity to histone chaperone Anti-silencing factor 1 (Asf1) that demonstrates off-target binding through low solubility (∼5 mg/mL) in the multivalent F(ab') 2 state...
July 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27222517/asf1-facilitates-dephosphorylation-of-rad53-after-dna-double-strand-break-repair
#19
Michael Tsabar, David P Waterman, Fiona Aguilar, Lizabeth Katsnelson, Vinay V Eapen, Gonen Memisoglu, James E Haber
To allow for sufficient time to repair DNA double-stranded breaks (DSBs), eukaryotic cells activate the DNA damage checkpoint. In budding yeast, Rad53 (mammalian Chk2) phosphorylation parallels the persistence of the unrepaired DSB and is extinguished when repair is complete in a process termed recovery or when the cells adapt to the DNA damage checkpoint. A strain containing a slowly repaired DSB does not require the histone chaperone Asf1 to resume cell cycle progression after DSB repair. When a second, rapidly repairable DSB is added to this strain, Asf1 becomes required for recovery...
May 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27036862/the-histone-chaperone-vps75-forms-multiple-oligomeric-assemblies-capable-of-mediating-exchange-between-histone-h3-h4-tetramers-and-asf1-h3-h4-complexes
#20
Colin M Hammond, Ramasubramanian Sundaramoorthy, Mark Larance, Angus Lamond, Michael A Stevens, Hassane El-Mkami, David G Norman, Tom Owen-Hughes
Vps75 is a histone chaperone that has been historically characterized as homodimer by X-ray crystallography. In this study, we present a crystal structure containing two related tetrameric forms of Vps75 within the crystal lattice. We show Vps75 associates with histones in multiple oligomers. In the presence of equimolar H3-H4 and Vps75, the major species is a reconfigured Vps75 tetramer bound to a histone H3-H4 tetramer. However, in the presence of excess histones, a Vps75 dimer bound to a histone H3-H4 tetramer predominates...
July 27, 2016: Nucleic Acids Research
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