Welcome back to Rad Onc Smart Review! This is Episode 35: DSB Repair Deep Dive: NHEJ & HRR Proteins. In our last episode, we explored how cells sense DNA damage and initiate signaling cascades. Today, we're diving into the critical repair mechanisms themselves, focusing on how cells mend the most dangerous of DNA lesions – double-strand breaks (DSBs). We'll compare and contrast the two major DSB repair pathways: Non-Homologous End Joining (NHEJ) and Homologous Recombination Repair (HRR), looking at their fidelity, template requirements, and cell cycle specificity. We'll then dissect the key protein players and the step-by-step processes involved in each pathway, and finally, discuss the clinical significance of defects in these pathways, particularly mutations in BRCA1 and BRCA2.