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Monoubiquitination

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https://www.readbyqxmd.com/read/28925810/ube3a-mediated-regulation-of-imprinted-genes-and-epigenome-wide-marks-in-human-neurons
#1
S Jesse Lopez, Keith Dunaway, M Saharul Islam, Charles Mordaunt, Annie Vogel Ciernia, Makiko Meguro-Horike, Shin-Ichi Horike, David J Segal, Janine LaSalle
The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A...
September 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28918480/sgs1-helicase-is-required-for-efficient-pcna-monoubiquitination-and-translesion-dna-synthesis-in-saccharomyces-cerevisiae
#2
Fangfang Li, Lindsay G Ball, Li Fan, Michelle Hanna, Wei Xiao
DNA-damage tolerance (DDT) is employed by eukaryotes to deal with replication blocks on the template strand, and is divided into two parallel pathways that are activated by sequential ubiquitination of proliferating cell nuclear antigen (PCNA) at the Lys164 residue. Rad6-Rad18-mediated PCNA monoubiquitination promotes translesion DNA synthesis (TLS) and the monoubiquitinated PCNA can be further polyubiquitinated by an Mms2-Ubc13-Rad5 complex, leading to error-free lesion bypass. We previously reported that the DNA helicase Sgs1 is required for error-free lesion bypass, probably through the double-Holliday junction migration and subsequent resolution...
September 16, 2017: Current Genetics
https://www.readbyqxmd.com/read/28886337/replication-fork-slowing-and-reversal-upon-dna-damage-require-pcna-polyubiquitination-and-zranb3-dna-translocase-activity
#3
Marko Vujanovic, Jana Krietsch, Maria Chiara Raso, Nastassja Terraneo, Ralph Zellweger, Jonas A Schmid, Angelo Taglialatela, Jen-Wei Huang, Cory L Holland, Katharina Zwicky, Raquel Herrador, Heinz Jacobs, David Cortez, Alberto Ciccia, Lorenza Penengo, Massimo Lopes
DNA damage tolerance during eukaryotic replication is orchestrated by PCNA ubiquitination. While monoubiquitination activates mutagenic translesion synthesis, polyubiquitination activates an error-free pathway, elusive in mammals, enabling damage bypass by template switching. Fork reversal is driven in vitro by multiple enzymes, including the DNA translocase ZRANB3, shown to bind polyubiquitinated PCNA. However, whether this interaction promotes fork remodeling and template switching in vivo was unknown. Here we show that damage-induced fork reversal in mammalian cells requires PCNA ubiquitination, UBC13, and K63-linked polyubiquitin chains, previously involved in error-free damage tolerance...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28865289/dna-polymerase-%C3%AE-the-long-and-the-short-of-it
#4
Ekaterina G Frank, Mary P McLenigan, John P McDonald, Donald Huston, Samantha Mead, Roger Woodgate
The cDNA encoding human DNA polymerase ι (POLI) was cloned in 1999. At that time, it was believed that the POLI gene encoded a protein of 715 amino acids. Advances in DNA sequencing technologies led to the realization that there is an upstream, in-frame initiation codon that would encode a DNA polymerase ι (polι) protein of 740 amino acids. The extra 25 amino acid region is rich in acidic residues (11/25) and is reasonably conserved in eukaryotes ranging from fish to humans. As a consequence, the curated Reference Sequence (RefSeq) database identified polι as a 740 amino acid protein...
August 19, 2017: DNA Repair
https://www.readbyqxmd.com/read/28859169/the-replication-initiator-protein-of-a-geminivirus-interacts-with-host-monoubiquitination-machinery-and-stimulates-transcription-of-the-viral-genome
#5
Nirbhay Kumar Kushwaha, Mansi Bhardwaj, Supriya Chakraborty
Geminiviruses constitute a group of plant viruses, with a ssDNA genome, whose replication in the nucleus of an infected cell requires the function of geminivirus-encoded replication initiator protein (Rep). Our results suggest that monoubiquitinated histone 2B (H2B-ub) promotes tri-methylation of histone 3 at lysine 4 (H3-K4me3) on the promoter of Chilli leaf curl virus (ChiLCV). We isolated homologues of two major components of the monoubiquitination machinery: UBIQUITIN-CONJUGATING ENZYME2 (NbUBC2) and HISTONE MONOUBIQUITINATION1 (NbHUB1) from N...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28855448/caffeine-has-a-synergistic-anticancer-effect-with-cisplatin-via-inhibiting-fanconi-anemia-group-d2-protein-monoubiquitination-in-hepatocellular-carcinoma-cells
#6
Yuichiro Oda, Muneaki Hidaka, Akito Suzuki
Cisplatin is an anticancer agent and induces DNA interstrand cross-links (ICLs). ICLs activate various signaling processes and induce DNA repair pathways, including the Fanconi anemia (FA) pathway. FA complementation group D2 (FANCD2) is monoubiquitinated in response to DNA damage, leading to activation of the DNA double-strand-break repair protein, RAD51. Caffeine increases the anticancer activity of cisplatin by inhibiting DNA repair; however, details of the mechanism remain unclear. We investigated the mechanism responsible for the synergistic anticancer effect of cisplatin and caffeine in HepG2 human hepatocellular carcinoma cells, focusing on the FA pathway...
August 31, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28841006/esi-im-ms-and-collision-induced-unfolding-that-provide-insight-into-the-linkage-dependent-interfacial-interactions-of-covalently-linked-diubiquitin
#7
Nicole D Wagner, David E Clemmer, David H Russell
Understanding protein higher order structure and interfacial interactions is crucial to understanding protein binding motifs and cellular function, that is, an interactome. Polyubiquitylation is a post-translational modification that functions as a tag for a diverse array of cellular processes, wherein differences in chain length, branching, and linkage site encode different cellular functions. Investigation of covalently linked diubiquitin (diUbq) molecules specifically selects for the effect of covalent linkage site on the conformational preference of the molecule and the interfacial interactions between the subunits...
August 31, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28837157/biallelic-truncating-fancm-mutations-cause-early-onset-cancer-but-not-fanconi-anemia
#8
Massimo Bogliolo, Dominique Bluteau, James Lespinasse, Roser Pujol, Nadia Vasquez, Catherine Dubois d'Enghien, Dominique Stoppa-Lyonnet, Thierry Leblanc, Jean Soulier, Jordi Surrallés
PurposeMutations in genes involved in Fanconi anemia (FA)/BRCA DNA repair pathway cause cancer susceptibility diseases including familial breast cancer and Fanconi anemia (FA). A single FA patient with biallelic FANCM mutations was reported in 2005 but concurrent FANCA pathogenic mutations precluded assignment of FANCM as an FA gene. Here we report three individuals with biallelic FANCM truncating mutations who developed early-onset cancer and toxicity to chemotherapy but did not present congenital malformations or any hematological phenotype suggestive of FA...
August 24, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28831681/neddylation-antagonizes-ubiquitination-of-proliferating-cell-nuclear-antigen-and-regulates-the-recruitment-of-polymerase-%C3%AE-in-response-to-oxidative-dna-damage
#9
Junhong Guan, Shuyu Yu, Xiaofeng Zheng
NEDDylation has been shown to participate in the DNA damage pathway, but the substrates of neural precursor cell expressed developmentally downregulated 8 (NEDD8) and the roles of NEDDylation involved in the DNA damage response (DDR) are largely unknown. Translesion synthesis (TLS) is a damage-tolerance mechanism, in which RAD18/RAD6-mediated monoubiquitinated proliferating cell nuclear antigen (PCNA) promotes recruitment of polymerase η (polη) to bypass lesions. Here we identify PCNA as a substrate of NEDD8, and show that E3 ligase RAD18-catalyzed PCNA NEDDylation antagonizes its ubiquitination...
August 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28825854/function-of-rad6b-and-rnf8-in-spermatogenesis
#10
Yingli Guo, Yanfeng Song, Zhao Guo, Mengjin Hu, Bing Liu, Hongyu Duan, Le Wang, Tianxia Yuan, Degui Wang
Histone ubiquitination regulates sperm formation and is important for nucleosome removal during spermatogenesis. RNF8 is an E3 ubiquitin ligase, and RAD6B is an E2 ubiquitin-conjugating enzyme. Both proteins participate in DNA damage repair processes via histone ubiquitination. Loss of RNF8 or RAD6B can lead to sterility in male mice. However, the specific mechanisms regulating these ubiquitin-mediated processes are unclear. In this study, we found that RNF8 knockout mice were either subfertile or sterile based on the numbers of offspring they produced...
August 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28778076/modulation-of-the-fanconi-anemia-pathway-via-chemically-induced-changes-in-chromatin-structure
#11
David A Vierra, Jada L Garzon, Meghan A Rego, Morganne M Adroved, Maurizio Mauro, Niall G Howlett
Fanconi anemia (FA) is a rare disease characterized by congenital defects, bone marrow failure, and atypically early-onset cancers. The FA proteins function cooperatively to repair DNA interstrand crosslinks. A major step in the activation of the pathway is the monoubiquitination of the FANCD2 and FANCI proteins, and their recruitment to chromatin-associated nuclear foci. The regulation and function of FANCD2 and FANCI, however, is poorly understood. In addition, how chromatin state impacts pathway activation is also unknown...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28761001/dna-damage-tolerance-in-hematopoietic-stem-and-progenitor-cells-in-mice
#12
Bas Pilzecker, Olimpia Alessandra Buoninfante, Paul van den Berk, Cesare Lancini, Ji-Ying Song, Elisabetta Citterio, Heinz Jacobs
DNA damage tolerance (DDT) enables bypassing of DNA lesions during replication, thereby preventing fork stalling, replication stress, and secondary DNA damage related to fork stalling. Three modes of DDT have been documented: translesion synthesis (TLS), template switching (TS), and repriming. TLS and TS depend on site-specific PCNA K164 monoubiquitination and polyubiquitination, respectively. To investigate the role of DDT in maintaining hematopoietic stem cells (HSCs) and progenitors, we used Pcna(K164R/K164R) mice as a unique DDT-defective mouse model...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28687786/involvement-of-fancd2-in-energy-metabolism-via-atp5%C3%AE
#13
Panneerselvam Jayabal, Chi Ma, Manoj Nepal, Yihang Shen, Raymond Che, James Turkson, Peiwen Fei
Growing evidence supports a general hypothesis that aging and cancer are diseases related to energy metabolism. However, the involvement of Fanconi Anemia (FA) signaling, a unique genetic model system for studying human aging or cancer, in energy metabolism remains elusive. Here, we report that FA complementation group D2 protein (FANCD2) functionally impacts mitochondrial ATP production through its interaction with ATP5α, whereas this relationship was not observed in the mutant FANCD2 (K561R)-carrying cells...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28669576/histone-h2a-monoubiquitination-in-neurodevelopmental-disorders
#14
REVIEW
Anshika Srivastava, Brian McGrath, Stephanie L Bielas
Covalent histone modifications play an essential role in gene regulation and cellular specification required for multicellular organism development. Monoubiquitination of histone H2A (H2AUb1) is a reversible transcriptionally repressive mark. Exchange of histone H2A monoubiquitination and deubiquitination reflects the succession of transcriptional profiles during development required to produce cellular diversity from pluripotent cells. Germ-line pathogenic variants in components of the H2AUb1 regulatory axis are being identified as the genetic basis of congenital neurodevelopmental disorders...
August 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28666371/the-identification-of-fancd2-dna-binding-domains-reveals-nuclear-localization-sequences
#15
Joshi Niraj, Marie-Christine Caron, Karine Drapeau, Stéphanie Bérubé, Laure Guitton-Sert, Yan Coulombe, Anthony M Couturier, Jean-Yves Masson
Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28636932/ubiquitination-linked-phosphorylation-of-the-fanci-s-tq-cluster-contributes-to-activation-of-the-fanconi-anemia-i-d2-complex
#16
Ronald S Cheung, Maria Castella, Antonio Abeyta, Philip R Gafken, Nyka Tucker, Toshiyasu Taniguchi
Repair of interstrand crosslinks by the Fanconi anemia (FA) pathway requires both monoubiquitination and de-ubiquitination of the FANCI/FANCD2 (FANCI/D2) complex. In the standing model, the phosphorylation of six sites in the FANCI S/TQ cluster domain occurs upstream of, and promotes, FANCI/D2 monoubiquitination. We generated phospho-specific antibodies against three different S/TQ cluster sites (serines 556, 559, and 565) on human FANCI and found that, in contrast to the standing model, distinct FANCI sites were phosphorylated either predominantly upstream (ubiquitination independent; serine 556) or downstream (ubiquitination-linked; serines 559 and 565) of FANCI/D2 monoubiquitination...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28604766/the-deubiquitinating-enzymes-usp4-and-usp17-target-hyaluronan-synthase-2-and-differentially-affect-its-function
#17
M Mehić, V K de Sa, S Hebestreit, C-H Heldin, P Heldin
The levels of hyaluronan, a ubiquitous glycosaminoglycan prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20). Hyaluronan accumulates in rapidly remodeling tissues, such as breast cancer, due to deregulated expression of the HAS2 gene and/or alterations of HAS2 activity. The activity of HAS2 is regulated by post-translational modifications, including ubiquitination. In order to identify deubiquitinating enzymes (DUBs) that are involved in de-ubiquitination of HAS2, a complementary (cDNA) library of 69 Flag-HA-tagged human DUBs cloned into retroviral vectors was screened in human embryonic kidney (HEK) 293T cells for their ability to de-ubiquitinate myc-tagged HAS2...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28596781/polycomb-group-proteins-ring1a-and-ring1b-regulate-the-vegetative-phase-transition-in-arabidopsis
#18
Jian Li, Zheng Wang, Yugang Hu, Ying Cao, Ligeng Ma
Polycomb group (PcG) protein-mediated gene silencing is a major regulatory mechanism in higher eukaryotes that affects gene expression at the transcriptional level. Here, we report that two conserved homologous PcG proteins, RING1A and RING1B (RING1A/B), are required for global H2A monoubiquitination (H2Aub) in Arabidopsis. The mutation of RING1A/B increased the expression of members of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) gene family and caused an early vegetative phase transition. The early vegetative phase transition observed in ring1a ring1b double mutant plants was dependent on an SPL family gene, and the H2Aub status of the chromatin at SPL locus was dependent on RING1A/B...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28536288/cnot4-mediated-ubiquitination-of-influenza-a-virus-nucleoprotein-promotes-viral-rna-replication
#19
Yu-Chen Lin, King-Song Jeng, Michael M C Lai
Influenza A virus (IAV) RNA segments are individually packaged with viral nucleoprotein (NP) and RNA polymerases to form a viral ribonucleoprotein (vRNP) complex. We previously reported that NP is a monoubiquitinated protein which can be deubiquitinated by a cellular ubiquitin protease, USP11. In this study, we identified an E3 ubiquitin ligase, CNOT4 (Ccr4-Not transcription complex subunit 4), which can ubiquitinate NP. We found that the levels of viral RNA, protein, viral particles, and RNA polymerase activity in CNOT4 knockdown cells were lower than those in the control cells upon IAV infection...
May 23, 2017: MBio
https://www.readbyqxmd.com/read/28535142/srs2-promotes-synthesis-dependent-strand-annealing-by-disrupting-dna-polymerase-%C3%AE-extending-d-loops
#20
Jie Liu, Christopher Ede, William D Wright, Steven K Gore, Shirin S Jenkins, Bret D Freudenthal, M Todd Washington, Xavier Veaute, Wolf-Dietrich Heyer
Synthesis-dependent strand annealing (SDSA) is the preferred mode of homologous recombination in somatic cells leading to an obligatory non-crossover outcome, thus avoiding the potential for chromosomal rearrangements and loss of heterozygosity. Genetic analysis identified the Srs2 helicase as a prime candidate to promote SDSA. Here, we demonstrate that Srs2 disrupts D-loops in an ATP-dependent fashion and with a distinct polarity. Specifically, we partly reconstitute the SDSA pathway using Rad51, Rad54, RPA, RFC, DNA Polymerase δ with different forms of PCNA...
May 23, 2017: ELife
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