The MRN complex is the initiation complex in theHR repair pathway. MRN complexes are rapidly recruited
to DSB sites, where they initiate DSB end resectionsand maintain DSB ends in preparation for subsequent
repair. In addition, ATM is recruited and activated tocoordinate DSB repair and cell cycle progression.42–44
ATM kinase activity in cells is initiated by intermolecular autophosphorylation at S1981, S367, and S1893.43 Theautophosphorylation of ATM enables it to dissociate intoactive monomer and be reactivated, enabling ATM toremain at DNA damage sites, where it catalyzes necessarydownstream phosphorylation events.41,43,45 When ATMis activated at DSBs, histone H2AX is phosphorylated toproduce H2AX, which then attracts and phosphorylatesMDC1 and activates two E3 ubiquitin ligases, RNF8 andRNF168, to start a ubiquitination (UB) cascade.2 Chromatin conformation changes caused by a series of signaling cascades promote the recruitment of multiple factors,including BRCA1, CtIP (MRX and Sae2 in yeast), EXO1,and BLM.46 The MRN complex and CtIP form complexeswith BRCA1, which is essential for facilitating DSB endresection.47,4
感謝中(zhōng)國湖南省(shěng)衡陽(yáng)市(shì)華南大學(xué)衡陽醫(yī)學院；北京(jīng)放射醫學研(yán)究(jiū)所北京(jīng)放(fàng)射生物學(xué)重點實(shí)驗室輻射生(shēng)物(wù)學(xué)係（中國(guó)北(běi)京）*通訊作(zuò)者(zhě)：高(gāo)珊珊，北京放射(shè)醫(yī)學(xué)研(yán)究(jiū)所北京放(fàng)射(shè)生(shēng)物學重點實驗室輻(fú)射生(shēng)物學係(xì)，引用文(wén)獻(xiàn)