ADP-ribosylation from molecular mechanisms to therapeutic implications

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4475 - 4495

Published: Oct. 1, 2023

ADP-ribosylation is a ubiquitous modification of biomolecules, including proteins and nucleic acids, that regulates various cellular functions in all kingdoms life. The recent emergence new technologies to study has reshaped our understanding the molecular mechanisms govern establishment, removal, recognition this modification, as well its impact on organismal function. These advances have also revealed intricate involvement human physiology pathology enormous potential their manipulation holds for therapy. In review, we present state-of-the-art findings covering work structural biology, biochemistry, cell clinical aspects ADP-ribosylation.

Language: Английский

---

Research progress of therapeutic drugs for doxorubicin-induced cardiomyopathy

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113903 - 113903

Published: Oct. 22, 2022

Doxorubicin (DOX), as a kind of chemotherapy agent with remarkable therapeutic effect, can be used to treat diverse malignant tumors clinically. Dose-dependent cardiotoxicity is the most serious adverse reaction after DOX treatment, which eventually leads cardiomyopathy and greatly limits clinical application DOX. DOX-induced not result single mechanistic action, multiple mechanisms have been discovered demonstrated experimentally, such oxidative stress, inflammation, mitochondrial damage, calcium homeostasis disorder, ferroptosis, autophagy apoptosis. Dexrazoxane (DEX) only protective approved by FDA for treatment cardiomyopathy, but its still has some limitations. Therefore, we need find other effective drugs soon possible. In this paper, that effectively improve in recent years are mainly described from aspects natural drugs, endogenous substances, new dosage forms, herbal medicines, chemical modification marketed drugs. The aim present study evaluate effects these on anticancer curative effects, so provide reference value future.

Language: Английский

---

Targeting the BRCA1/2 deficient cancer with PARP inhibitors: Clinical outcomes and mechanistic insights

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: March 22, 2023

BRCA1 and BRCA2 play a critical role in variety of molecular processes related to DNA metabolism, including homologous recombination mediating the replication stress response. Individuals with mutations ( BRCA1/2 ) genes have significantly higher risk developing various types cancers, especially cancers breast, ovary, pancreas, prostate. Currently, Food Drug Administration (FDA) has approved four PARP inhibitors (PARPi) treat mutations. In this review, we will first summarize clinical outcomes FDA-approved PARPi treating deficient cancers. We then discuss evidence supporting hypothesis that cytotoxic effect is likely due inducing excessive at difficult-to-replicate (DTR) genomic regions mutated tumors. Finally, ongoing preclinical studies on how combine immuno-oncology drugs further improve outcomes.

Language: Английский

---

EXO1 protects BRCA1-deficient cells against toxic DNA lesions

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(4), P. 659 - 674.e7

Published: Jan. 23, 2024

Inactivating mutations in the BRCA1 and BRCA2 genes impair DNA double-strand break (DSB) repair by homologous recombination (HR), leading to chromosomal instability cancer. Importantly, BRCA1/2 deficiency also causes therapeutically targetable vulnerabilities. Here, we identify dependency on end resection factor EXO1 as a key vulnerability of BRCA1-deficient cells. generates poly(ADP-ribose)-decorated lesions during S phase that associate with unresolved DSBs genomic but not wild-type or BRCA2-deficient Our data indicate BRCA1/EXO1 double-deficient cells accumulate due impaired single-strand annealing (SSA) top their HR defect. In contrast, retain SSA activity absence hence tolerate loss. Consistent EXO1-mediated SSA, find BRCA1-mutated tumors show elevated expression increased SSA-associated scars compared BRCA1-proficient tumors. Overall, our findings uncover promising therapeutic target for

Language: Английский

---

Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(4)

Published: April 1, 2024

It is well known that DNA damage can cause apoptosis. However, whether apoptosis and its metabolites contribute to repair largely unknown. In this study, we found apoptosis-deficient Fas

Language: Английский

---

Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(10), P. 1743 - 1760.e11

Published: April 27, 2023

PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon damage, it was unknown whether this signal plays active role in cell or is just byproduct poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies sensitive and flexible detection mono-ADP-ribosylation, fluorescence-based sensors live-cell imaging, we demonstrate serine constitutes second wave PARP1 signaling shaped by HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone readers, RNF114, ubiquitin ligase recruited to lesions through zinc-finger domain, modulating damage response telomere maintenance. Our work provides technological framework illuminating ADP-ribosylation wide range applications biological contexts establishes important information carrier signaling.

Language: Английский

---

Role of condensates in modulating DNA repair pathways and its implication for chemoresistance

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(6), P. 104800 - 104800

Published: May 9, 2023

For cells, it is important to repair DNA damage, such as double-strand and single-strand breaks, because unrepaired can compromise genetic integrity, potentially leading cell death or cancer. Cells have multiple damage pathways that been the subject of detailed genetic, biochemical, structural studies. Recently, scientific community has started gain evidence breaks may occur within biomolecular condensates also contribute through concentrating genotoxic agents used treat various cancers. Here, we summarize key features note where they implicated in breaks. We describe suggesting be involved other types including nucleotide modifications (e.g., mismatch oxidized bases), bulky lesions, among others. Finally, discuss old new mysteries could now addressed considering properties condensates, chemoresistance mechanisms. Chemical changes highly harmful living organisms. DNA, like molecules, undergo chemical reactions. These reactions spontaneously a result exposure chemicals radiation (1Lindahl T. Instability decay primary structure DNA.Nature. 1993; 362: 709-715Crossref PubMed Scopus (4388) Google Scholar). When these altered structure, base excision block gene expression replication negatively affecting homeostasis, function, survival (2Alhmoud J.F. Woolley Al Moustafa A.E. Malki M.I. damage/repair management cancers.Cancers (Basel). 2020; 121050Crossref (96) Thus, promptly properly repaired by cells allow for organism survival. Decades investigation into shed light on diverse cellular responsible resolve damage. include (BER), (NER), homologous recombination (HR), (MMR), non-homologous end joining (NHEJ) (3Chatterjee N. Walker G.C. Mechanisms repair, mutagenesis.Environ. Mol. Mutagen. 2017; 58: 235-263Crossref (801) Scholar, 4Huang R. Zhou P.K. repair: historical perspectives, mechanistic clinical translation targeted cancer therapy.Signal. Transduct Target. Ther. 2021; 6: 254Crossref (121) Dozens different proteins must efficiently recruited at sites work coordination proper repair. Structure-based studies revealed interacting portions recruitment lesions (5Perry J.J. Cotner-Gohara E. Ellenberger Tainer J.A. Structural dynamics signaling repair.Curr. Opin. Struct. Biol. 2010; 20: 283-294Crossref (41) 6Bigot Day M. Baldock R.A. Watts F.Z. Oliver A.W. Pearl L.H. Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 9-1-1 control G1 checkpoint.Elife. 2019; 8e44353Crossref (23) 7Sun Y. McCorvie T.J. Yates L.A. Zhang X. basis recombination.Cell. Life Sci. 77: 3-18Crossref (54) 8Blackford A.N. Jackson S.P. ATM, ATR, DNA-PK: trinity heart response.Mol. Cell. 66: 801-817Abstract Full Text PDF 9McPherson K.S. Korzhnev D.M. Targeting protein-protein response chemotherapy.RSC Chem. 2: 1167-1195Crossref 10Cleary J.M. Aguirre A.J. Shapiro G.I. D'Andrea A.D. Biomarker-guided development inhibitors.Mol. 78: 1070-1085Abstract (113) Moreover, great emphasis recently put disordered regions molecules shared function subcellular compartments not enclosed membranes, called (11Spegg V. Altmeyer Biomolecular damage: more than just phase.DNA Repair (Amst). 106103179Crossref (25) 12Jiang S. Fagman J.B. Chen C. Alberti Liu B. Protein phase separation its role tumorigenesis.Elife. 9e60264Crossref 13Tong Tang Xu J. Wang W. Zhao Yu et al.Liquid-liquid tumor biology.Signal. Transduct. Target 2022; 7: 221Crossref (9) In this review, focus involvement open questions field condensate properties. A emerging study biology consists identification characterization condensates. Condensates are defined sub-cellular physically membranes concentrate (including nucleic acids) (14Sabari B.R. Dall'Agnese A. Young nucleus.Trends Biochem. 45: 961-977Abstract (148) 15Conti B.A. Oppikofer condensates: opportunities drug discovery RNA therapeutics.Trends Pharmacol. 43: 820-837Abstract Scholar) compartmentalize biochemical 16Banani S.F. Lee H.O. Hyman A.A. Rosen M.K. organizers biochemistry.Nat. Rev. Cell 18: 285-298Crossref (2427) 17Harrison A.F. Shorter RNA-binding prion-like domains health disease.Biochem. 474: 1417-1438Crossref (252) 18Shin Brangwynne C.P. Liquid condensation physiology disease.Science. 357eaaf4382Crossref (1651) The first observed were Nucleolus (19Sirri Urcuqui-Inchima Roussel P. Hernandez-Verdun D. Histochem. 2008; 129: 13-31Crossref (308) Cajal bodies (20Morris G.E. Body.Biochim. Biophys. Acta. 1783: 2108-2115Crossref Thanks advancement microscopy technologies growing interest those compartments, many discovered, transcriptional (21Sabari Boija Klein I.A. Coffey E.L. Shrinivas K. al.Coactivator super-enhancers links control.Science. 2018; 361eaar3958Crossref 22Shrinivas Sabari Zamudio A.V. al.Enhancer drive formation condensates.Mol. 75: 549-561.e547Abstract (193) Scholar), nuclear speckles (23Spector D.L. Lamond A.I. Nuclear speckles.Cold Spring Harb. Perspect. 2011; 3a000646Crossref (539) splicing (24Guo Y.E. Manteiga J.C. Henninger J.E. Hannett N.M. al.Pol II phosphorylation regulates switch between condensates.Nature. 572: 543-548Crossref (317) constitutive heterochromatin (25Keenen M.M. Brown Brennan L.D. Renger Khoo H. Carlson C.R. al.HP1 compact mechanically positionally stable separated domains.Elife. 10e64563Crossref (37) 26Strom A.R. Emelyanov Mir Fyodorov D.V. Darzacq Karpen G.H. Phase drives domain formation.Nature. 547: 241-245Crossref (993) 27Larson A.G. Elnatan Keenen Trnka M.J. Johnston Burlingame A.L. al.Liquid droplet HP1α suggests heterochromatin.Nature. 236-240Crossref (926) stress granules (28Brangwynne Eckmann Courson D.S. Rybarska Hoege Gharakhani al.Germline P liquid droplets localize controlled dissolution/condensation.Science. 2009; 324: 1729-1732Crossref (1614) (29Gao X.K. Rao X.S. Cong X.X. Sheng Z.K. Sun Y.T. S.B. al.Phase insulin receptor substrate 1 insulin/IGF-1 signalosomes.Cell Discov. 8: 60Crossref (5) 30Su Ditlev Hui Xing Banjade Okrut promotes T signal transduction.Science. 2016; 352: 595-599Crossref (625) 31Ditlev Vega Koster Su Tani Lakoduk A.M. al.A composition-dependent molecular clutch actin.Elife. 8e42695Crossref (56) 32Zamudio Afeyan L.K. al.Mediator factors identity genes.Mol. 76: 753-766.e756Abstract (112) 33Jaqaman membrane signaling.Curr. 69: 48-54Crossref (0) 34Case L.B. Regulation transmembrane separation.Annu. 48: 465-494Crossref (139) 35Zeng Guan Wu Tong al.Reconstituted postsynaptic density platform understanding synapse plasticity.Cell. 174: 1172-1187Abstract (211) 36Lin Suen Jeffrey Wieteska L. Stainthorp Seiler al.Receptor tyrosine kinases regulate transduction liquid–liquid state.bioRxiv. ([preprint])https://doi.org/10.1101/783720Crossref 37Huang W.Y.C. Alvarez Kondo Y.K. Chung J.K. Lam H.Y.M. assembly transition kinetic proofreading modulate Ras activation SOS.Science. 363: 1098-1103Crossref 38Zeng Shang Araki Guo Huganir R.L. densities underlies synaptic complexes 166: 1163-1175Abstract (300) 39Dall'Agnese Platt Zheng Friesen G. Blaise al.The dynamic clustering disrupted resistance.Nat. Commun. 13: 7522Crossref (1) pore (40Hampoelz Schwarz Ronchi Bragulat-Teixidor Tischer Gaspar I. al.Nuclear pores assemble from nucleoporin during Oogenesis.Cell. 179: 671-686Abstract (45) miRNA processing (41Lee S.C. Martienssen plant processing.Nat. 23: 5-6Crossref (2) (DDR) 42Kilic Lezaja Gatti Bianco Michelena Imhof determines liquid-like behavior compartments.EMBO 38e101379Crossref (205) 43Vítor A.C. Sridhara Sabino Afonso Grosso Martin R.M. al.Single-molecule imaging transcription damaged chromatin.Sci. Adv. 5eaau1249Crossref (32) 44Capozzo Iannelli F. Francia d'Adda di Fagagna Express repress? dilemma chromatin.FEBS 284: 2133-2147Crossref (22) (Fig. 1). physicochemical suggest functions (45Alberti Gladfelter Mittag Considerations challenges studying liquid-liquid condensates.Cell. 176: 419-434Abstract (1065) fast adaptive responses environment. They buffer concentrations proteins; activate reactions; sequester inactivate their specific viscoelastic properties, generate mechanical forces. act filters, example, nucleopore which permit deny entry nucleus (30Su 45Alberti 46Li C.H. al.MeCP2 neurodevelopmental disease.Nature. 586: 440-444Crossref (77) 47Schmidt H.B. Görlich Transport selectivity pores, separation, membraneless organelles.Trends 41: 46-61Abstract (267) Among physical models explain how formed, one them Liquid-Liquid Separation (LLPS) (48Hyman Weber C.A. Jülicher Liquid-liquid biology.Annu. Dev. 2014; 30: 39-58Crossref LLPS described thermodynamically driven phenomenon consisting de-mixing solution two distinct phases. 1940s, Flory Huggins ability polymers, proteins, self-organize discrete (49Flory P.J. Thermodynamics high polymer solutions.J. Phys. 1941; 9: 423-432Crossref (1278) 50Huggins M.L. Solutions long chain compounds.J. 440Crossref over last 10 years, essential life shown able form dense phases resembling 21Sabari 24Guo 51Henninger Oksuz O. Sagi LeRoy al.RNA-mediated feedback 184: 207-225.e224Abstract (175) 52Chatterjee Maltseva Kan Hosseini Gonella Bonn al.Lipid-driven interfacial ordering FUS.Sci. 8eabm7528Crossref dividing milieu "condensed phase" "dilute 2). Considering potential impact biomedical field, determine what leads generation compartments. Over suggested promoted several factors, protein (51Henninger 53Dignon G.L. Best R.B. Mittal separation: driving forces macroscopic properties.Annu. 71: 53-75Crossref (177) Different known promote formation, structured intrinsically (IDRs)/low complexity (LCDs) play behaviors, IDRs studied disease contexts (54Darling Oldfield C.J. Uversky V.N. Intrinsically proteome human membrane-less organelles.Proteomics. 18e1700193Crossref (119) There IDRs, elastin-like polypeptides (55Muiznieks Sharpe Pomès Keeley F.W. Role elastin extracellular matrix proteins.J. 430: 4741-4753Crossref (57) (56Kim H.J. Kim N.C. Y.D. Scarborough E.A. Moore Diaz Z. al.Mutations hnRNPA2B1 hnRNPA1 cause multisystem proteinopathy ALS.Nature. 2013; 495: 467-473Crossref (1023) enriched charged amino acids (57Miyagi Yamazaki Ueda Narumi Hayamizu Uji I.H. patterning proportion residues arginine-rich mixed-charge organelle protein.Int. 7658Crossref 58Uversky Gillespie J.R. Fink Why "natively unfolded" unstructured under physiologic conditions?.Proteins. 2000; 415-427Crossref Several tried investigate relevance IDR composition formation. seem preferentially partners show similar characteristics behavior, charge–charge hydrophobic (59Lyons Veettil R.T. Pradhan Fornero De La Cruz Ito al.Functional partitioning regulators patterned charge blocks.Cell. 2023; 186: 327-345.e328Abstract importance protein–protein reasonable think would possible artificially design will alter therapeutic purposes. Kameda colleagues designed small peptides either impaired p53 vitro. This approach taken peptide-therapeutics (60Kamagata Ariefai Takahashi Hando Subekti D.R.G. Ikeda al.Rational peptide regulating residue-residue contact energy.Sci. Rep. 1213718Crossref only drivers Indeed, roles promoting (61Ilık İ Aktaş speckles: hubs regulation.FEBS 289: 7234-7245Crossref (28) (62Wheeler Matheny Jain Abrisch Parker Distinct stages granule disassembly.Elife. 5e18413Crossref (409) Notably, there controlling dissolution (63Sharp P.A. Chakraborty A.K. regulation condensates.RNA. 28: 52-57Crossref (13) interact IDRs. One example RNA-mediated model proposed transcribed RNAs, short enhancer-RNA, initially stimulate increasing weak multivalent components appears favor until overall zero (charge-balance model). At point, further both enhancer-RNA pre-mRNA, condensate. subdomains SH3 (64Amaya Ryan V.H. Fawzi N.L. Fyn kinase interacts induces low-complexity hnRNPA2.J. 293: 19522-19531Abstract (27) α-helical (65Conicella Dignon Zerze Schmidt D'Ordine Y.C. al.TDP-43 tunes function.Proc. Natl. Acad. U. 117: 5883-5894Crossref (152) Genomic constantly subjected endogenous environmental threats, oxidative stress, alkylation, UV-damage, chemotherapeutics, so on. threats incorrectly mutations chromosomal rearrangements aberrations. alterations lead genomic instability, pathologies, ranging neurodegenerative diseases (66Postel-Vinay Vanhecke Olaussen K.A. Lord Ashworth Soria exploiting DNA-repair defects optimizing lung treatment.Nat. Clin. Oncol. 2012; 144-155Crossref (89) 67Hanahan Weinberg Hallmarks cancer: next generation.Cell. 144: 646-674Abstract (44586) recognition (or tolerance) lesions. together, an orchestra, playing symphony DDR cell-type-, cell-cycle stage- chromatin context-dependent manner (68Vaddavalli P.L. Schumacher network: systemic aging.Trends Genet. 38: 598-612Abstract 69Jackson Bartek DNA-damage 461: 1071-1078Crossref (3969) 70Polo S.E. Dynamics breaks: modifications.Genes 25: 409-433Crossref (844) 71van Attikum Gasser S.M. Crosstalk histone response.Trends 19: 207-217Abstract (416) 72Yasuhara Zou Impacts compartmentalization repair.DNA 105103162Crossref (4) three main classes pathways. class single level non-distorting BER pathway. pathway repairs majority alkylating damages removal base. It (SSBs) PARP (73Caldecott K.W. break disease.Trends 32: 733-745Abstract 74Saville K.M. Clark Wilk Rogers G.D. Andrews Koczor al.NAD(+)-mediated mammalian 93102930Crossref 75Caldecott Mammalian dancing moonlight.DNA 93102921Crossref second includes NER pathway, repairing distorting deriving adducts UV-induced excising degrading stretch ssDNA containing then restoring correct nucleotides polymerization-dependent (76Apelt Lans Schärer O.D. Luijsterburg M.S. Nucleotide leaves mark chromatin: detection nucleosomes.Cell. 7925-7942Crossref (12) 77Duan Speer Ulibarri K.J. Mao Transcription-coupled insights approaches.DNA 103103126Crossref (11) 78Krasikova Rechkunova Lavrik Neurological Abnormalities.Int. 22: 6220Crossref third MMR, whose polymerase misincorporation errors ensuring highest fidelity process. MMR replacement strand 3). usually originate following: (i) mismatches occurring replication; (ii) minority G, (iii) bulges repeated oligonucleotide sequences, trinucleotide expansion (79Elez Mismatch preserving genome

Language: Английский

---

Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 187, P. 106314 - 106314

Published: Oct. 1, 2023

Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of PARP superfamily, with its primary function being facilitation DNA damage repair processes. Parthanatos a type regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including accumulation ADP-ribose polymers (PAR), binding PAR and apoptosis-inducing factor (AIF), release AIF from mitochondria, translocation AIF/macrophage migration inhibitory (MIF) complex, massive MIF-mediated fragmentation. Over past few decades, role in central nervous system health disease has received increasing attention. In this review, we discuss biological functions neural proliferation differentiation, memory formation, brain ageing, epigenetic regulation. We then elaborate on involvement PARP-1-dependant parthanatos various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications initiation, progression, therapeutic opportunities for different neurological illnesses, neurodegenerative diseases, stroke, autism spectrum disorder (ASD), sclerosis (MS), epilepsy, neuropathic pain (NP). Finally, emerging insights into repurposing inhibitors management diseases are provided. This review aims to summarize exciting advancements critical disorders, may open new avenues options targeting or parthanatos.

Language: Английский

---

PARP1 roles in DNA repair and DNA replication: The basi(c)s of PARP inhibitor efficacy and resistance

Seminars in Oncology, Journal Year: 2023, Volume and Issue: 51(1-2), P. 2 - 18

Published: Sept. 6, 2023

Genome integrity is under constant insult from endogenous and exogenous sources. In order to cope, eukaryotic cells have evolved an elaborate network of DNA repair that can deal with diverse lesion types exhibits considerable functional redundancy. PARP1 a major sensor breaks established putative roles in number pathways within the network, including single- double-strand as well protection replication fork. Importantly, target small-molecule PARP inhibitors (PARPi), which are employed treatment homologous recombination (HR)-deficient tumors, latter particularly susceptible accumulation damage due inability efficiently highly toxic breaks. The clinical success PARPi has fostered extensive research into biology, shed light on involvement various genomic transactions. A goal field been understand relationship between catalytic inhibition trapping. specific consequences trapping stability basis for cytotoxicity remain matter debate. Finally, increasingly recognized its capacity elicit/modulate anti-tumor immunity. potential is, however, hindered by development resistance. Hence, efforts invested identifying factors promote resistance or sensitize PARPi. current review provides summary advances our understanding mechanistic nature, molecular inhibition, mechanisms give rise

Language: Английский

---

PARP14 is a writer, reader, and eraser of mono-ADP-ribosylation

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(9), P. 105096 - 105096

Published: July 26, 2023

PARP14/BAL2 is a large multidomain enzyme involved in signaling pathways with relevance to cancer, inflammation, and infection. Inhibition of its mono-ADP-ribosylating PARP homology domain three ADP-ribosyl binding macro domains has been regarded as potential means therapeutic intervention. Macrodomains-2 -3 are known stably bind ADP-ribosylated target proteins, but the function macrodomain-1 remained somewhat elusive. Here, we used biochemical assays ADP-ribosylation levels characterize PARP14 homologous PARP9. Our results show that both macrodomains display an glycohydrolase activity not directed toward specific protein side chains. unable degrade poly(ADP-ribose), enzymatic product PARP1. The F926A mutation F244A PARP9 strongly reduced respective macrodomains, suggesting mechanistic Mac1 SARS-CoV-2 Nsp3 protein. This study adds two new enzymes previously six human glycohydrolases. have key implications for how will be studied their functions understood.

Language: Английский

---