2025
SMARCA5 restricts chromatin accessibility to promote male meiosis and fertility in mammals
Kataruka S, Malla A, Rainsford S, Walters B, Heuer R, Marshall K, Lesch B. SMARCA5 restricts chromatin accessibility to promote male meiosis and fertility in mammals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2422356122. PMID: 40743397, PMCID: PMC12337329, DOI: 10.1073/pnas.2422356122.Peer-Reviewed Original ResearchConceptsMale germ cellsChromatin accessibilityChromatin remodelingMale meiosisTranscriptional statesGerm cellsPachytene stageMeiotic prophaseDNA repairMeiotic gene transcriptionMeiotic prophase progressionSingle cell RNA sequencingPachytene stage of meiosis IStages of spermatogenic developmentCell RNA sequencingElevated rates of apoptosisTransposon controlSperm formationPremeiotic spermatogoniaRate of apoptosisStages of meiosis IChromosome synapsisMeiotic recombinationAbnormal spermatocytesSpermatogenic developmentFAM72A promotes UNG2 degradation and mutagenesis in human cancer cells
Feng Y, Barbulescu P, Chana C, Shirdarreh M, Yang H, Wu L, Mamand S, Kashem M, Zia A, Han M, Tsao J, Pugh T, Cescon D, Schatz D, Sicheri F, Martin A, Pezo R. FAM72A promotes UNG2 degradation and mutagenesis in human cancer cells. Scientific Reports 2025, 15: 23467. PMID: 40604025, PMCID: PMC12223117, DOI: 10.1038/s41598-025-07723-x.Peer-Reviewed Original ResearchConceptsUracil DNA glycosylase 2Proteasomal degradationMutagenic repairMutagenic DNA repairFunctional roleTumorigenic tissuesBase excision repairHuman cancer cellsSubstrate adaptorHuman cell linesE3 ligaseBioinformatics studiesDNA repairGenetic lesionsExcision repairHuman cellsCancer cellsCell linesHuman biologyFAM72AMechanisms of carcinogenesisCancer developmentProtein levelsGenesFAM72Protein–Protein Interactions in Base Excision Repair
Rathnaiah G, Sweasy J. Protein–Protein Interactions in Base Excision Repair. Biomolecules 2025, 15: 890. PMID: 40563529, PMCID: PMC12190888, DOI: 10.3390/biom15060890.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA RepairDNA Repair EnzymesExcision RepairHumansProtein BindingProtein Interaction MapsConceptsProtein-protein interactionsBase excision repairPolynucleotide kinase-phosphataseApurinic/apyrimidinic endonuclease 1X-ray repair cross-complementing protein 1Single-nucleotide base excision repairBase excision repair componentsExcision repairDNA polymerase BBase excision repair pathwayRepair of damaged basesDNA repair processesCore enzymePolymerase BDNA intermediatesProtein-proteinDamaged basesSingle-nucleotideDNA glycosylaseMolecular networksMolecular underpinningsDNAFunctional evidenceProtein 1EnzymeH3.1K27M-induced misregulation of the TONSOKU-H3.1 pathway causes genomic instability
Yuan W, Huang Y, LeBlanc C, Poulet A, De Luna Vitorino F, Valsakumar D, Dean R, Garcia B, van Wolfswinkel J, Voigt P, Jacob Y. H3.1K27M-induced misregulation of the TONSOKU-H3.1 pathway causes genomic instability. Nature Communications 2025, 16: 3547. PMID: 40229276, PMCID: PMC11997104, DOI: 10.1038/s41467-025-58892-2.Peer-Reviewed Original ResearchConceptsGenomic instabilityChromatin-based mechanismsHistone mark H3K27me3DNA damageH3K27MChromatin maturityGenome integrityNascent chromatinCell identityHistone H3Transcriptional programsH3.1 variantsGenomic alterationsDNAGenomeHistoneH3K27M expressionTumors of patientsEctopic activityATXR5ATXR6ExpressionCellsChromatinDNA lesions piece together impossible trees
Arnedo-Pac C, Aitken S. DNA lesions piece together impossible trees. Trends In Genetics 2025, 41: 456-458. PMID: 40180876, DOI: 10.1016/j.tig.2025.03.002.Peer-Reviewed Original Researchp53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells
Miller K, Li B, Pierce-Hoffman H, Patel S, Lei X, Rajesh A, Teneche M, Havas A, Gandhi A, Macip C, Lyu J, Victorelli S, Woo S, Lagnado A, LaPorta M, Liu T, Dasgupta N, Li S, Davis A, Korotkov A, Hultenius E, Gao Z, Altman Y, Porritt R, Garcia G, Mogler C, Seluanov A, Gorbunova V, Kaech S, Tian X, Dou Z, Chen C, Passos J, Adams P. p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells. Nature Communications 2025, 16: 2229. PMID: 40044657, PMCID: PMC11882782, DOI: 10.1038/s41467-025-57229-3.Peer-Reviewed Original ResearchConceptsCytoplasmic chromatin fragmentsDNA repairGenome integrityChromatin fragmentsNuclear DNA damage signalsGenomic instabilitySenescent cellsActivation of p53Controlling DNA repairATM-dependent mannerDNA damage signalingSignatures of agingAge-associated accumulationActivate p53P53 activationHallmarks of agingDamage signalingAge-associated diseasesSignaling circuitsP53Molecular circuitsEnhanced DNA repairGenomePharmacological inhibitionAge-associated inflammation
2024
Strand-resolved mutagenicity of DNA damage and repair
Anderson C, Talmane L, Luft J, Connelly J, Nicholson M, Verburg J, Pich O, Campbell S, Giaisi M, Wei P, Sundaram V, Connor F, Ginno P, Sasaki T, Gilbert D, López-Bigas N, Semple C, Odom D, Aitken S, Taylor M. Strand-resolved mutagenicity of DNA damage and repair. Nature 2024, 630: 744-751. PMID: 38867042, PMCID: PMC11186772, DOI: 10.1038/s41586-024-07490-1.Peer-Reviewed Original ResearchConceptsDNA damageDNA damage-induced mutationsSingle-base resolutionCancer genome evolutionDamage-induced mutationsRepair of DNA damageNucleotide excision repairGenome evolutionMultiple distinct mutationsDNA accessibilityGenomic conditionsReplicative strandProcess genomesDNA base damageTranslesion polymerasesExcision repairDNAMutation patternsMutationsBase damageRepair efficiencyStrandsAlkyl adductsReplicationIdentity fidelitySingle-mitosis dissection of acute and chronic DNA mutagenesis and repair
Ginno P, Borgers H, Ernst C, Schneider A, Behm M, Aitken S, Taylor M, Odom D. Single-mitosis dissection of acute and chronic DNA mutagenesis and repair. Nature Genetics 2024, 56: 913-924. PMID: 38627597, PMCID: PMC11096113, DOI: 10.1038/s41588-024-01712-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA DamageDNA RepairHumansMiceMitosisMutagenesisMutationReactive Oxygen SpeciesUltraviolet RaysConceptsMutational processesUV damageGenome evolutionGenome-wideTranscribed regionsGenome replicationCancer genomesUV mutationCC dinucleotidesDNA mutagenesisSister cellsDriving evolutionGenomeMutagenesisPunctuated burstsSingle cellsRounds of genome replicationMutationsStrandsCellsMitosisDinucleotideSisterROSReplication
2023
H3.1K27me1 loss confers Arabidopsis resistance to Geminivirus by sequestering DNA repair proteins onto host genome
Wang Z, Castillo-González C, Zhao C, Tong C, Li C, Zhong S, Liu Z, Xie K, Zhu J, Wu Z, Peng X, Jacob Y, Michaels S, Jacobsen S, Zhang X. H3.1K27me1 loss confers Arabidopsis resistance to Geminivirus by sequestering DNA repair proteins onto host genome. Nature Communications 2023, 14: 7484. PMID: 37980416, PMCID: PMC10657422, DOI: 10.1038/s41467-023-43311-1.Peer-Reviewed Original ResearchConceptsDNA repair proteinsDNA repair pathwaysRepair pathwaysRepair proteinsWild-type plantsDefense-related genesArabidopsis resistanceHeterochromatin amplificationHeterochromatic regionsRAD51 recruitmentRep proteinGenomic instabilityHealthy plantsUnstable genomeHost genomeATXR6GeminivirusesRobust resistanceProteinViral amplificationGenomeMutantsViral DNATransposonPlantsLysine Demethylation in Pathogenesis
Cao J, Yan Q. Lysine Demethylation in Pathogenesis. Advances In Experimental Medicine And Biology 2023, 1433: 1-14. PMID: 37751133, DOI: 10.1007/978-3-031-38176-8_1.ChaptersConceptsLysine demethylasesLSD1/KDM1AHistone lysine methylationHistone lysine methyltransferasesMajor epigenetic mechanismsNormal developmentNon-histone substratesSpecific small molecule inhibitorsSmall molecule inhibitorsLysine methylationLysine methyltransferasesHistone methylationHistone lysineLysine demethylationEpigenetic mechanismsDNA repairArginine residuesHuman diseasesMore subfamiliesMolecule inhibitorsLysine modificationDemethylasesMethylationTreatment of cancerEnzymeQuantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markersAcetylation of MLH1 by CBP increases cellular DNA mismatch repair activity
Zhang M, Zhao J, Glazer P, Bai W, Bepler G, Zhang X. Acetylation of MLH1 by CBP increases cellular DNA mismatch repair activity. The Journal Of Biochemistry 2023, 174: 183-191. PMID: 37094360, DOI: 10.1093/jb/mvad034.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationCREB-Binding ProteinDNADNA Mismatch RepairDNA RepairProtein Processing, Post-TranslationalConceptsMutLα complexMMR activityUbiquitin-proteasome degradation pathwayDNA mismatch repair activityDNA damage responsePost-translational modificationsCell cycle checkpointsOverexpression of CBPMismatch repair activityDNA base pair mismatchesInsertions/deletionsDNA mismatch repair proteinsGenomic integrityDamage responseDNA replicationCycle checkpointsRepair proteinsTrichostatin ABase pair mismatchesNovel roleMismatch repair proteinsRepair activityCBPProteinDeacetylase inhibitors
2022
Metastatic and multiply relapsed SDH‐deficient GIST and paraganglioma displays clinical response to combined poly ADP‐ribose polymerase inhibition and temozolomide
Singh C, Bindra RS, Glazer PM, Vasquez JC, Pashankar F. Metastatic and multiply relapsed SDH‐deficient GIST and paraganglioma displays clinical response to combined poly ADP‐ribose polymerase inhibition and temozolomide. Pediatric Blood & Cancer 2022, 70: e30020. PMID: 36151992, DOI: 10.1002/pbc.30020.Peer-Reviewed Original ResearchBRCA2 BRC missense variants disrupt RAD51-dependent DNA repair
Jimenez-Sainz J, Mathew J, Moore G, Lahiri S, Garbarino J, Eder JP, Rothenberg E, Jensen RB. BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair. ELife 2022, 11: e79183. PMID: 36098506, PMCID: PMC9545528, DOI: 10.7554/elife.79183.Peer-Reviewed Original ResearchMeSH KeywordsBRCA2 ProteinDNA RepairDNA, Single-StrandedMutation, MissenseNucleoproteinsRad51 RecombinaseConceptsHomology-directed repairDNA double-strand breaksFork protectionReplication fork protectionRad51 nucleoprotein filamentsMissense mutationsSingle amino acid substitutionRad51-ssDNA complexesDouble-strand breaksUnknown functional consequencesBRCA2 VUSAmino acid substitutionsGenome stabilityNucleoprotein filamentDNA repairRepeat regionSpacer regionBRCA2 proteinBenign allelesCellular responsesAcid substitutionsFunctional consequencesFrameshift mutationGene predisposeBRC2Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1
Skoko J, Cao J, Gaboriau D, Attar M, Asan A, Hong L, Paulsen C, Ma H, Liu Y, Wu H, Harkness T, Furdui C, Manevich Y, Morrison C, Brown E, Normolle D, Spies M, Spies M, Carroll K, Neumann C. Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1. Redox Biology 2022, 56: 102443. PMID: 36058112, PMCID: PMC9450138, DOI: 10.1016/j.redox.2022.102443.Peer-Reviewed Original ResearchConceptsRAD51 foci formationFoci formationRedox regulationHomologous recombination DNA repair pathwayHR DNA repairProtein binding partnersPoly (ADP-ribose) polymeraseDNA repair pathwaysDAz-2Rad51 proteinSensitization of cellsRad51 filamentsBinding partnerHomologous recombinationDNA repairCysteine oxidationRepair pathwaysMediator proteinsHuman breast cancer cellsCellular responsesPeroxiredoxin 1Breast cancer cellsDNA damagePRDX1Cys319Mechanism-based design of agents that selectively target drug-resistant glioma
Lin K, Gueble SE, Sundaram RK, Huseman ED, Bindra RS, Herzon SB. Mechanism-based design of agents that selectively target drug-resistant glioma. Science 2022, 377: 502-511. PMID: 35901163, PMCID: PMC9502022, DOI: 10.1126/science.abn7570.Peer-Reviewed Original ResearchThe histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication
Davarinejad H, Huang YC, Mermaz B, LeBlanc C, Poulet A, Thomson G, Joly V, Muñoz M, Arvanitis-Vigneault A, Valsakumar D, Villarino G, Ross A, Rotstein BH, Alarcon EI, Brunzelle JS, Voigt P, Dong J, Couture JF, Jacob Y. The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication. Science 2022, 375: 1281-1286. PMID: 35298257, PMCID: PMC9153895, DOI: 10.1126/science.abm5320.Peer-Reviewed Original ResearchConceptsTetratricopeptide repeat domainDNA polymerase thetaMulticellular eukaryotesHistone H3.1Replication forksChromatin maturationRepeat domainDNA repairGenomic instabilityPolymerase thetaPosition 31Amino acidsH3.1PlantsReplicationEukaryotesH3.3HistonesMonomethylationVariantsCommon strategyForkResiduesMaturationFunctionOncometabolites as Regulators of DNA Damage Response and Repair
Gueble SE, Bindra RS. Oncometabolites as Regulators of DNA Damage Response and Repair. Seminars In Radiation Oncology 2022, 32: 82-94. PMID: 34861999, DOI: 10.1016/j.semradonc.2021.09.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA damage responseDamage responseDDR defectsMultiple DNA repair pathwaysSynthetic lethal interactionsDNA repair pathwaysRepair pathwaysLethal interactionsDiverse mechanismsOncometaboliteCancer therapyCertain cancersNew mechanismTherapeutic strategiesSmall intermediatesBiologyRegulatorPathwayMechanismRepairDDRMetabolismDysregulationDefectsResponse
2021
Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair
Dow J, Krysztofiak A, Liu Y, Colon-Rios DA, Rogers FA, Glazer PM. Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair. Molecular Cancer Research 2021, 19: 2057-2067. PMID: 34535560, PMCID: PMC8642278, DOI: 10.1158/1541-7786.mcr-21-0456.Peer-Reviewed Original ResearchConceptsHistone deacetylase inhibitor vorinostatPatient-derived tumor xenograftsHomology-directed repairIsocitrate dehydrogenase 1/2 mutationsHistone deacetylase inhibitionIDH1 mutant cellsGreater cell deathHDACi treatmentInhibitor vorinostatTumor xenograftsDeacetylase inhibitionIDH1/2 mutationsPotential biomarkersSpecific cancersMutant cancersCancerCancer cellsDNA repair defectsMalignancyVorinostatDNA double-strand breaksGliomasHistone hypermethylationCell deathPARPiRegulation of the Cell-Intrinsic DNA Damage Response by the Innate Immune Machinery
Hayman TJ, Glazer PM. Regulation of the Cell-Intrinsic DNA Damage Response by the Innate Immune Machinery. International Journal Of Molecular Sciences 2021, 22: 12761. PMID: 34884568, PMCID: PMC8657976, DOI: 10.3390/ijms222312761.Peer-Reviewed Original ResearchMeSH KeywordsDNA DamageDNA RepairHumansImmunity, InnateMembrane ProteinsNucleotidyltransferasesSignal TransductionConceptsDNA double-strand breaksInnate immune machineryGenomic integrityDNA-damaging therapiesDNA damage response systemDNA DSB repair pathwaysImmune machineryCell-autonomous responsesDNA damage responseDSB repair pathwaysDouble-strand breaksDamage responseInnate immune pathwaysRepair pathwaysCell survivalDNA damageUnderappreciated roleProper repairImmune pathwaysMachineryPathwayAdaptive immune responsesSignificant normal tissue toxicityMost therapeutic studiesImmune response
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