2018
Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair
Sulkowski PL, Sundaram RK, Oeck S, Corso CD, Liu Y, Noorbakhsh S, Niger M, Boeke M, Ueno D, Kalathil AN, Bao X, Li J, Shuch B, Bindra RS, Glazer PM. Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nature Genetics 2018, 50: 1086-1092. PMID: 30013182, PMCID: PMC6072579, DOI: 10.1038/s41588-018-0170-4.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksPGL/PCCDNA repair deficiency syndromeHomologous recombination DNA repair pathwayDNA repair pathwaysDouble-strand breaksHomologous recombination DNA repairSynthetic lethal targetingGenomic integrityDNA repairFumarate hydrataseMechanistic basisCancer predispositionFunction mutationsGermline lossKrebs cycleSuccinate dehydrogenaseHereditary paragangliomaRespectively1–3Ribose polymerase inhibitorsHereditary leiomyomatosisHereditary cancer syndromesCancer syndromesTumor cellsPolymerase inhibitors
2017
DNA polymerase beta participates in DNA End-joining
Ray S, Breuer G, DeVeaux M, Zelterman D, Bindra R, Sweasy JB. DNA polymerase beta participates in DNA End-joining. Nucleic Acids Research 2017, 46: 242-255. PMID: 29161447, PMCID: PMC5758893, DOI: 10.1093/nar/gkx1147.Peer-Reviewed Original ResearchConceptsDouble-strand breaksAlternative NHEJHomologous recombinationDNA polymerasePol βX-family DNA polymerasesFamily DNA polymerasesDNA polymerase betaDNA pol βDeleterious lesionsDNA endsGenomic instabilityNHEJ pathwayDNA proteinProcessing enzymesDefective repairCellular sensitivityCell deathStrand breaksPolymerase betaSubunit inhibitorPolymeraseSmall deletionsMechanistic insightsNHEJ
2016
A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin
Janssen A, Breuer GA, Brinkman EK, van der Meulen AI, Borden SV, van Steensel B, Bindra RS, LaRocque JR, Karpen GH. A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin. Genes & Development 2016, 30: 1645-1657. PMID: 27474442, PMCID: PMC4973294, DOI: 10.1101/gad.283028.116.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksHomologous recombinationGenome stabilityHeterochromatic DSBsEuchromatic DSBsSingle DNA double-strand breakMain DSB repair pathwaysDifferent chromatin domainsLarval imaginal discsDistinct nuclear domainsRepetitive DNA sequencesDSB repair pathwaysDouble-strand breaksChromatin contextChromatin domainsEuchromatic lociPericentromeric heterochromatinChromatin regionsHomologous chromosomesHR templateImaginal discsDSB repairDNA sequencesNuclear domainsRepair pathways
2015
Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors
Goglia AG, Delsite R, Luz AN, Shahbazian D, Salem AF, Sundaram RK, Chiaravalli J, Hendrikx PJ, Wilshire JA, Jasin M, Kluger HM, Glickman JF, Powell SN, Bindra RS. Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors. Molecular Cancer Therapeutics 2015, 14: 326-342. PMID: 25512618, PMCID: PMC4326563, DOI: 10.1158/1535-7163.mct-14-0765.Peer-Reviewed Original ResearchConceptsDSB repair inhibitorsDouble-strand breaksDSB repairHomologous recombinationRepair inhibitorsCell-based small molecule screenSuccessful DSB repairDNA-damaging agentsPlate-based formatCell-based screenSmall-molecule screenGenomic integrityTumor cell survivalMammalian cellsHR repairDNA repairMolecule screenReporter systemSecondary assaysCell survivalDNA damageCancer cell linesTumor cellsNovel hitsMost cancer therapies
2009
Targeting the DNA damage response for cancer therapy
Powell SN, Bindra RS. Targeting the DNA damage response for cancer therapy. DNA Repair 2009, 8: 1153-1165. PMID: 19501553, DOI: 10.1016/j.dnarep.2009.04.011.Peer-Reviewed Original ResearchConceptsDNA damage responseCell cycle checkpointsDouble-strand breaksGenome integrityGenomic integrityHistone modificationsDamage responseCycle checkpointsDNA repairKey proteinsDNA damageAnti-cancer agentsHuman tumorsNew anti-cancer agentsPathwayCancer therapyTumor cellsCheckpointProteinTherapeutic interventionsRepairIntegrityDefectsCellsAppropriate response