Seeonlineversionforlegendandreferences.496Cell142,August6,2010©2010ElsevierInc.DOI10.1016/j.cell.2010.07.035SnapShot:NonhomologousDNAEndJoining(NHEJ)MichaelR.Lieber1andThomasE.Wilson21UniversityofSouthernCalifornia,LosAngeles,CA90089,USAand2UniversityofMichigan,AnnArbor,MI48109,USAMichaelR.Lieber1andThomasE.Wilson21UniversityofSouthernCalifornia,LosAngeles,CA90089,USAand2UniversityofMichigan,AnnArbor,MI48109,USASnapShot:NonhomologousDNAEndJoining(NHEJ)MichaelR.Lieber1andThomasE.Wilson21UniversityofSouthernCalifornia,LosAngeles,CA90089,USAand2UniversityofMichigan,AnnArbor,MI48109,USA496.e1Cell142,August6,2010©2010ElsevierInc.DOI10.1016/j.cell.2010.07.035Double-strandbreaks(DSBs)areseriousgeneticlesionsthatmustberepairedtopreventcatastrophiclossofchromosomes.Ingeneral,twoclassesofmechanismsexistforrepairingdouble-strandbreaks,homologousrecombination(HR)ornonhomologousendjoining(NHEJ).HRrequiresanidentical(ornearlyidentical)templatestrandofDNAtomendalesionwhereasNHEJrepairsadouble-strandgapinDNAwithoutahomologoustemplate(middleupperpanel).NHEJ,however,isnotentirelydevoidofguidinginformation.Shortstretchesofcomplementary“microhomology”sequences(1–10basepairs)oftenappearatrepairjunc-tions,suggestingthatlimitedbasepairingbetweentwoendsofadouble-strandbreakisexploitedduringrepair.Thus,NHEJisguidedentirelybyinformationinthelesion,whichmakesNHEJerrorproneincomparisontoHR.Nonetheless,NHEJisoptimalandnecessaryfordouble-strandbreakrepairduringthecell-cyclestages(i.e.,G0andG1)whensis-terchromatidsarenotavailabletoguidemoreaccuraterepairbyHR.Mostnotably,NHEJisincrediblyflexibleintermsofitssubstratesandrepairmechanisms.InthisSnapShot,wedescribethewiderangeoflesionsonwhichNHEJoperates,thediversemechanismsusedtojointhesebreaks,andthemanyoutcomespossibleattherepairedjunctions.ManyPathwaysManystressescausedouble-strandbreaksinDNA.Theseincludeionizingradiation,reactiveoxygenspecies(ROS),mechanicalstress,failureoftopoisomeraseenzymeactivity,andreplicationacrossnicksordamagedDNA....
