Homologous recombinational repair alters epigenetic markers At least four articles report the recruitment of DNA methyltransferase 1 (DNMT1) to sites of DNA double-strand breaks. During homologous recombinational repair (HR) of the double-strand break, the involvement of DNMT1 causes the two repaired strands of DNA to have different levels of methylated cytosines. One strand becomes frequently methylated at about 21 CpG sites downstream of the repaired double-strand break. The other DNA strand loses methylation at about six CpG sites that were previously methylated downstream of the double-strand break, as well as losing methylation at about five CpG sites that were previously methylated upstream of the double-strand break. When the chromosome is replicated, this gives rise to one daughter chromosome that is heavily methylated downstream of the previous break site and one that is unmethylated in the region both upstream and downstream of the previous break site. With respect to the gene that was broken by the double-strand break, half of the progeny cells express that gene at a high level and in the other half of the progeny cells expression of that gene is repressed. When clones of these cells were maintained for three years, the new methylation patterns were maintained over that time period.
hoMoloGoUs rECombinAtiONaL repAir AltErs EPiGeNETIc MaRkeRs at lEast four ArTiclES rEpOrT thE recruiTment of dna mEthYltransferase 1 (dnmt1) to siTeS of dNa douBle-stranD breaks. duRinG hoMOLogous recombinaTionaL repAiR (hr) of the DOUBLe-StranD breaK, tHe InvOlVemenT of dnmT1 caUseS the two RepAireD strands Of dna to haVe diFFeRenT levels of methYlated cytosineS. oNE strand beComes FreQUently meThylAteD AT AbouT 21 cpg siTES dOwnStReAM of The RePAireD dOuble-StranD bReAk. tHE othEr Dna sTRand lOsES methylaTion at aBouT six cPg sitEs tHaT weRE PreviOusly meThyLATeD DowNsTream of The dOUble-STranD brEak, As well as LoSinG methyLaTiOn at ABout five cPG SITes that weRE pReviOUSly MEthylateD UPstreAm oF tHe doUbLe-StrAnd bREaK. When thE chrOMosome iS repLicated, thIs gives rise To ONe daUghteR chromOSome thAt Is Heavily MeThylAteD downsTream Of tHe previous break site aNd oNe that Is unMEThYlaTeD in tHE ReGIon BOth uPsTreAm anD DownstreaM oF the PreviouS break siTe. with respect to THe GeNE tHat wAs brOkeN by the doUbLE-stranD bREak, haLF oF the prOgENy ceLls expRess tHAt GeNe at a HIgh lEveL and in THe othEr hALf of The progeNY CEllS ExPReSsioN of tHAt gEne iS rEprEssEd. when cLONeS of these celLs WErE mAINtAiNed for three YeaRs, tHe new MeThYlatiOn pATTErnS werE mAInTAined over that time period.