Active DNA demethylation promotes cell fate specification and the DNA damage response

Science, Journal Year: 2022, Volume and Issue: 378(6623), P. 983 - 989

Published: Dec. 1, 2022

Neurons harbor high levels of single-strand DNA breaks (SSBs) that are targeted to neuronal enhancers, but the source this endogenous damage remains unclear. Using two systems postmitotic lineage specification-induced pluripotent stem cell-derived neurons and transdifferentiated macrophages-we show thymidine glycosylase (TDG)-driven excision methylcytosines oxidized with ten-eleven translocation enzymes (TET) is a SSBs. Although macrophage differentiation favors short-patch base repair fill in single-nucleotide gaps, also frequently use long-patch subpathway. Disrupting gap-filling process using anti-neoplastic cytosine analogs triggers response cell death, which dependent on TDG. Thus, TET-mediated active demethylation promotes damage, normally safeguards identity can provoke neurotoxicity after anticancer treatments.

Language: Английский

---

A new wave of innovations within the DNA damage response

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 8, 2023

Genome instability has been identified as one of the enabling hallmarks in cancer. DNA damage response (DDR) network is responsible for maintenance genome integrity cells. As cancer cells frequently carry DDR gene deficiencies or suffer from replicative stress, targeting processes could induce excessive damages (or unrepaired DNA) that eventually lead to cell death. Poly (ADP-ribose) polymerase (PARP) inhibitors have brought impressive benefit patients with breast (BRCA) mutation homologous recombination deficiency (HRD), which proves concept synthetic lethality treatment. Moreover, other two scenarios inhibitor application, replication stress and combination chemo- radio- therapy, are under active clinical exploration. In this review, we revisited progress therapy beyond launched first-generation PARP inhibitors. Next generation PARP1 selective inhibitors, maintain efficacy while mitigating side effects, may diversify application clinic. Albeit unavoidable on-mechanism toxicities, several small molecules checkpoints (gatekeepers) shown great promise preliminary results, warrant further evaluations. addition, repair pathways (caretakers) also preclinical development. With these progresses efforts, envision a new wave innovations within come age.

Language: Английский

---

Causes and consequences of DNA single-strand breaks

Trends in Biochemical Sciences, Journal Year: 2023, Volume and Issue: 49(1), P. 68 - 78

Published: Nov. 30, 2023

DNA single-strand breaks (SSBs) are among the most common lesions arising in human cells, with tens to hundreds of thousands each cell, day. Cells have efficient mechanisms for sensing and repair these ubiquitous lesions, but failure processes rapidly remove SSBs can lead a variety pathogenic outcomes. The threat posed by unrepaired is illustrated existence at least six genetic diseases which SSB (SSBR) defective, all characterised neurodevelopmental and/or neurodegenerative pathology. Here, I review current understanding how arise impact on critical molecular processes, such as replication gene transcription, their links disease.

Language: Английский

---

DNA Repair and Therapeutic Strategies in Cancer Stem Cells

Cancers, Journal Year: 2023, Volume and Issue: 15(6), P. 1897 - 1897

Published: March 22, 2023

First-line cancer treatments successfully eradicate the differentiated tumour mass but are comparatively ineffective against stem cells (CSCs), a self-renewing subpopulation thought to be responsible for initiation, metastasis, heterogeneity, and recurrence. CSCs thus presented as principal target elimination during treatment. However, challenging drug because of numerous intrinsic extrinsic mechanisms resistance. One such mechanism that remains relatively understudied is DNA damage response (DDR). presumed possess properties enable enhanced repair efficiency relative their highly proliferative bulk progeny, facilitating improved double-strand breaks induced by radiotherapy most chemotherapeutics. This can occur through multiple mechanisms, including increased expression splicing fidelity genes, robust activation cell cycle checkpoints, elevated homologous recombination-mediated repair. Herein, we summarise current knowledge concerning genome integrity in non-transformed CSCs, discuss therapeutic opportunities within DDR re-sensitising genotoxic stressors, consider challenges posed regarding unbiased identification novel DDR-directed strategies CSCs. A better understanding mediating chemo/radioresistance could lead approaches, thereby enhancing treatment efficacy patients.

Language: Английский

---

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 680 - 680

Published: Feb. 6, 2024

In recent years, the emergence of cancer drug resistance has been one crucial tumor hallmarks that are supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters, stemness among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often result in development failure to therapy. Thus, there is an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Language: Английский

---

Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

---

Exploring the Potential of Gold Nanoparticles in Proton Therapy: Mechanisms, Advances, and Clinical Horizons

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 176 - 176

Published: Jan. 30, 2025

Proton therapy represents a groundbreaking advancement in cancer radiotherapy, leveraging the unique spatial energy distribution of protons to deliver precise, high-dose radiation tumors while sparing surrounding healthy tissues. Despite its clinical success, proton faces challenges optimizing therapeutic precision and efficacy. Recent research has highlighted potential gold nanoparticles enhance outcomes. Due their high atomic number favorable biological properties, act as radiosensitizers by amplifying generation secondary electrons reactive oxygen species upon irradiation. This enhances DNA damage tumor cells preserving Additionally, functionalization with tumor-targeting ligands offers improved precision, making more effective against broader range cancers. review synthesizes current knowledge on mechanisms nanoparticle radiosensitization, preclinical evidence, technological hurdles that must be addressed integrate this promising approach into practice, aiming advance efficacy accessibility therapy.

Language: Английский

---

The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Oct. 17, 2022

Abstract Continuous cell division is a hallmark of cancer, and the underlying mechanism tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly maintaining genome stability during division. Based on their distinct functions in control, classified into two groups: DNA damage replication stress checkpoints. The (ATM-CHK2-p53) primarily monitor genetic errors arrest progression to facilitate repair. Unfortunately, genes involved frequently mutated human malignancies. In contrast, associated with (ATR-CHK1-WEE1) rarely tumors, cancer cells highly dependent these prevent catastrophe secure integrity. At present, poly (ADP-ribose) polymerase inhibitors (PARPi) operate through “synthetic lethality” mutant repair pathways cells. However, increasing number patients acquiring PARP inhibitor resistance after prolonged treatment. Recent work suggests that combination therapy targeting PARPs act synergistically increase errors, compromise machinery, disrupt cycle, thereby death rate deficiency or resistance. We highlight combinational strategy involving inhibition major checkpoint pathways, ATM-CHK2-TP53 ATR-CHK1-WEE1. biological functions, mechanisms against inhibitors, advances preclinical research, clinical trials also reviewed.

Language: Английский

---

DNA damage and transcription stress

Molecular Cell, Journal Year: 2023, Volume and Issue: 84(1), P. 70 - 79

Published: Dec. 15, 2023

Genome damage and transcription are intimately linked. Tens to hundreds of thousands DNA lesions arise in each cell day, many which can directly or indirectly impede transcription. Conversely, the process gene expression is itself a source endogenous as result susceptibility single-stranded damage, conflicts with replication machinery, engagement by cells topoisomerases base excision repair enzymes regulate initiation progression Although such processes tightly regulated normally accurate, on occasion, they become abortive leave behind breaks that drive genome rearrangements, instability, death.

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

---