Skip to main content
. Author manuscript; available in PMC: 2022 Dec 1.
Published in final edited form as: Pharmacol Ther. 2021 Jun 23;228:107922. doi: 10.1016/j.pharmthera.2021.107922

Figure 2. TMZ induced double strands breaks addressed by Homologous Repair.

Figure 2.

Unrepaired O6-meG adducts will lead to DSB, which is the most lethal DNA damage. DSB can be sensed by the MRE11-RAD50-NBS1 (MRN complexes), which set in motion a numbers of processes collectively called the DNA damage response to coordinate DNA repair, These sensor complexes recruit and activate kinases including ATM, ATR, DNA-PK and subsequently other modifying enzymes which, through cascades of phosphorylation and ubiquitination events, activate and mobilize a large number of proteins, such as p53, BRCA1, 53BP1 and H2AX. Homologous Repair requires resection by BRCA1, CtIP and BARD1 to generate single-stranded DNA (ssDNA), which immediately becomes coated by RPA and subsequently replaced by Rad51 preparing for strand invasion. Failure of Homologous Repair will result in cell death.