2024
Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency
Goehring L, Keegan S, Lahiri S, Xia W, Kong M, Jimenez-Sainz J, Gupta D, Drapkin R, Jensen R, Smith D, Rothenberg E, Fenyö D, Huang T. Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency. Nature Communications 2024, 15: 4716. PMID: 38830843, PMCID: PMC11148086, DOI: 10.1038/s41467-024-48286-1.Peer-Reviewed Original ResearchConceptsTranscription termination sitesTranscription-replication conflictsDormant originsReplication stressElongating RNA polymerase IITermination sitesResponse to replication stressRNA polymerase IIR-loop formationTumor suppressor proteinPolymerase IIR-loopsLong genesRNase H2Transcription initiationOK-seqGenomic sitesSuppressor proteinCellular genomeBRCA2 deficiencyOrigin firingSuper-resolution microscopyGenomic instabilityDormant origin firingTranscription
2020
Binding of FANCD2 to SRSF1 Splicing Factor Prevents Genomic Instability through R Loop Regulation
Olazabal-Herrero A, Green A, Chen X, Sung P, Pillai M, Kupfer G. Binding of FANCD2 to SRSF1 Splicing Factor Prevents Genomic Instability through R Loop Regulation. Blood 2020, 136: 19. DOI: 10.1182/blood-2020-141369.Peer-Reviewed Original ResearchR-loopsFA pathwayGenomic instabilityFanconi anemiaSplicing factorsR-loop metabolismR-loop regulationFA-like phenotypeBasic cellular processesR-loop formationKey regulatory stepNon-canonical roleDNA damaging agentsNon-canonical mechanismFANCD2-FANCIGenome maintenanceFANCD2 monoubiquitinationMRNA exportGenomic sitesCellular processesInsect cellsProcessing proteinsFA phenotypeRNA transcriptionRegulatory step
2019
RNA–DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission Yeast
Hu Y, Bennett HW, Liu N, Moravec M, Williams JF, Azzalin CM, King MC. RNA–DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission Yeast. Genetics 2019, 213: 431-447. PMID: 31405990, PMCID: PMC6781888, DOI: 10.1534/genetics.119.302606.Peer-Reviewed Original ResearchConceptsTelomeric repeat-containing RNAHomology-directed repairFission yeastR-loopsLinear chromosomesTelomere maintenanceRecombination-based telomere maintenanceTelomerase-independent telomere maintenanceShelterin component Rap1State of telomeresTelomeric R-loopsRepeat-containing RNARNA-DNA hybridsDeletion of Rap1Telomerase-independent mechanismChromosome endsShelterin componentsGrowth crisisTelomerase functionTelomeric DNARecombination factorsSubset of cancersTelomeresAlternative lengtheningShort telomeresBinding of FANCI-FANCD2 Complex to RNA and R-Loops Stimulates Robust FANCD2 Monoubiquitination
Liang Z, Liang F, Teng Y, Chen X, Liu J, Longerich S, Rao T, Green AM, Collins NB, Xiong Y, Lan L, Sung P, Kupfer GM. Binding of FANCI-FANCD2 Complex to RNA and R-Loops Stimulates Robust FANCD2 Monoubiquitination. Cell Reports 2019, 26: 564-572.e5. PMID: 30650351, PMCID: PMC6350941, DOI: 10.1016/j.celrep.2018.12.084.Peer-Reviewed Original ResearchConceptsR-loopsCo-transcriptional R-loopsFANCI-FANCD2 complexFanconi anemiaR-loop structuresSeries of RNADNA replicative stressGuanine-rich sequencesFANCD2 monoubiquitinationGenomic lociID2 complexReplicative stressFA cellsRNA transcriptionFA pathwayComplex bindsDNA hybridsCancer predispositionBone marrow failureDNA damageRNAMonoubiquitinationDevelopmental abnormalitiesMarrow failureSsRNA
2017
A mitosis-specific and R loop–driven ATR pathway promotes faithful chromosome segregation
Kabeche L, Nguyen HD, Buisson R, Zou L. A mitosis-specific and R loop–driven ATR pathway promotes faithful chromosome segregation. Science 2017, 359: 108-114. PMID: 29170278, PMCID: PMC5875943, DOI: 10.1126/science.aan6490.Peer-Reviewed Original ResearchConceptsFaithful chromosome segregationChromosome segregationR-loopsATR pathwayCyclin-dependent kinase 1 (CDK1) activityWhole chromosome missegregationReplication stress responseReplication protein ADNA damage responseCentromere protein FKinase 1 activityATR functionAurora BDamage responseChromosome instabilityCentromeresProtein FAtaxia telangiectasiaAurora AUnexpected roleStress responseDNA damageDNA synthesisATRProtein A
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