Figure 6.3

Mechanism of nonhomologous (illegitimate) recombination at sites of double strand breakage in DNA. The ends are sites of association of end-binding proteins, Ku70, Ku86, and p450 DNA-dependent kinase. After limited exonucleolytic degradation, short single stranded DNA termini (that may not necessarily be from either side of the original break) with a few nucleotides that can form base-pairs will hybridize and local regions can then be patched by DNA polymerase b and ligase. The extent of sequence overlap is very short, usually less than 10 nucleotides (more often 1 to about 5). The p450 kinase interacts with p53 and initiates intracellular signal transduction pathways.

radon exposure in which all damaged cells receive single alpha-particle tracks and the maximal track length through the nucleus is still below the D37 dose required for cell-killing. More important, even at low doses, is whether any kinds of damage are completely irreparable and whether repair is always accurate. Persistent genetic changes caused by radiation must then be caused by repair that misassembles broken termini from distant regions of the genome and triggers a lasting genetic instability.

Homologous rejoining involves matching of a broken fragment with the corresponding region on the undamaged homologous chromosome followed by strand invasion and reconstruction of the damaged region by replication of the sequence information in the intact homologue (figure 6.2). It requires that the two homologues are within range of each other; consequently, it might be more important for replicating cells in late S and G2 phases of the cell cycle when sister chromatids are in close apposition (Takata and others in press; Sonoda and others 1998; Thompson 1996) and contributes to increased radio-resistance in these phases of the cell cycle (Cheong and others 1994). This form of double-strand repair is likely to be highly accurate because of the use of sequence information from the intact chromosomal homologue (chromatid) in reconstructing the broken DNA. The Rad51 protein

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