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. 2020 May 11;12(5):1206. doi: 10.3390/cancers12051206

Figure 2.

Figure 2

(A) Homologous recombination. A DNA double strand break is sensed and recognized by the MRE11-RAD50-NBS1 complex (MRN). The binding of this complex activates ATM kinase that leads to the activation of DNA damage response. Nuclease activity leads to end resection from 5′ to 3′ that then leads to the formation of single-strand DNA ends coated by phosphorylated RPA (pRPA). The exposed single strand DNA activates ATR’s response to facilitate the repair. This leads to the activation of BRCA/BRCA2/PALB2 complex which prepares RAD51 nucleofilaments for loading on DNA. The RAD51 nucleoprotein filament is loaded by BRCA2/PALB2 on the homology sequence and the RAD51 coated strand along with BRCA2/PALB2 mediates strand invasion and D loop formation. This also releases the MRE11-RAD50-NBS1 complex and the double stranded breaks are restored by branch migration, DNA synthesis and ligation. (B) Stalled replication forks are protected by the BRCA1/BRCA2/PALB2 complex with RAD51 loading onto the nascent DNA. This protects from end resection by MRE11 and other proteins to allow fork restart.