MEDRADSC 2X03 Chapter Notes - Chapter 2: Telophase, Nuclear Matrix, Nucleolus
Document Summary
Several dna-dna and dna-protein crosslinks induced by ionizing radiation have not been extensively studied to arrive at a quantitative estimate. Furthermore, the genes and pathways used for dna-dna or dna- protein crosslink repair are still under investigation. The current thinking is that a combination of ner and recombinational repair pathways is needed to repair dna crosslinks (fig. The predominant signal from a dna- interstrand crosslink that signals for repair is stalling of the dna replication fork. The crosslink is removed in a multistep process, first from one strand by a second round of ner, resulting in a strand break and a dna adduct. Dna synthesis can proceed past the lesion, resulting in a point mutation opposite the lesion. However, the ssb will become a dsb, and seems to require hrr for restitution. Finally, the adduct that remains is removed by ner. Cells with mutations in ner and hrr pathways are modestly sensitive to crosslinking agents.