Replication of chromosomal and episomal DNA in X-ray-damaged human cells: a cis- or trans-acting mechanism?
Episomal plasmids and viruses in mammalian cells present small targets for X-ray-induced DNA damage. At doses up to 100 Gy, DNA strand breaks or endonuclease III-sensitive sites were not discernible in 10.3-kb Epstein-Barr virus-based plasmid DNA or in 4.9-kb defective simian virus 40 DNA. DNA replication in these small molecules, however, was inhibited strongly by X-ray doses of greater than or equal to 20 Gy, decreasing to only 20 to 40% of control values. Inhibition was relieved slightly by growth in caffeine but was increased by growth in 3-aminobenzamide. Inhibition of DNA replication in episomal DNA molecules that are too small to sustain significant damage directly to their DNA may be due to either (a) a trans-acting diffusible factor that transfers the consequences of DNA breakage to episomes and to other replicating molecules, (b) a cis-acting mechanism in which episomes are structurally linked to genomic chromatin, and replication of both episomal and chromosomal replicons is under common control, or (c) radiation damage on other cellular structures unrelated to DNA. The resolution of these cellular mechanisms may shed light on the X-ray-resistant replication in ataxia-telangiectasia and may suggest strategies for molecular characterization of potential trans- or cis-acting factors.
Cleaver
J E
JE
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143-0750.
Rose
R
R
Mitchell
D L
DL
D001549:Benzamides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002875:Chromosomes / Q000528:radiation effects*; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004261:DNA Replication / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004706:Endodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010957:Plasmids / Q000528:radiation effects*; D013539:Simian virus 40; D014965:X-Rays
D001549:Benzamides; D002110:Caffeine; C025160:3-aminobenzamide; D004247:DNA; D004706:Endodeoxyribonucleases