The mechanism by which X rays inhibit DNA replication has been investigated in three distinct populations of DNA molecules in human cells: (a) large chromosomal DNA, (b) a population of 50-100 10.3-kb nuclear episomal plasmids per cell, and (c) a population of about 500 16-kb cytoplasmic mitochondrial DNA molecules per cell. DNA replication was inhibited by X rays in nuclear chromosomal and plasmid DNA, but not in mitochondrial DNA. The mechanism by which ionizing radiation inhibits DNA replication must therefore be nuclear-specific and is unlikely to involve diffusible low-molecular-weight substances. Since mitochondrial DNA exists in the cell as independent 16-kb circular molecules and responds to radiation as would be expected for small targets, the implication for nuclear plasmids is that their replication is regulated by a large target. A current model for DNA replication involves the movement of DNA through replication centers made up of polymerases, helicases, and associated replication enzymes that are attached to a matrix. The difference in the response to X rays between mitochondrial DNA and nuclear plasmid DNA can be explained if nuclear plasmids are tightly associated with chromosomal DNA and attached to the matrix, and are coordinately replicated.
Replication of Nuclear and Mitochondrial DNA in X-Ray-Damaged Cells: Evidence for a Nuclear-Specific Mechanism That Down-Regulates Replication
- Views Icon Views
- Share Icon Share
- Search Site
J. E. Cleaver; Replication of Nuclear and Mitochondrial DNA in X-Ray-Damaged Cells: Evidence for a Nuclear-Specific Mechanism That Down-Regulates Replication. Radiat Res 1 September 1992; 131 (3): 338–344. doi: https://doi.org/10.2307/3578425
Download citation file: