Coordination of DNA–PK Activation and Nuclease Processing of DNA Termini in NHEJ

摘要: Abstract DNA double-strand breaks (DSB), particularly those induced by ionizing radiation (IR), are complex lesions that can be cytotoxic if not properly repaired. IR-induced DSB often have termini modifications, including thymine glycols, ring fragmentation, 3′-phosphoglycolates, 5′-hydroxyl groups, and abasic sites. Nonhomologous end joining (NHEJ) is a major pathway responsible for the repair of these breaks. Proteins involved in NHEJ include Ku 70/80 heterodimer, DNA–PKcs, processing proteins Artemis polymerases μ λ, XRCC4, ligase IV, XLF. We will discuss role physical functional interactions DNA–PK as result activation, with an emphasis on structure, chemistry, sequence. With diversity IR DSB, it becoming increasingly clear multiple enzymes likely necessary effective break. explore roles several important enzymes, focus nuclease...