Aldehyde-induced protein-DNA crosslinks disrupt specific stages of SV40 DNA replication.
Aldehydes with specific protein-DNA crosslinking ability disrupted simian virus 40 (SV40) DNA replication to cause replication fork failure by the 40S intermediate pathway, in which replicating viral genomes become inactivated and torsionally stressed. In contrast, aldehydes without detectable protein-DNA crosslinking ability had no effect on SV40 DNA replication during the 10 min exposure times employed. This indicates that protein-DNA crosslinks block either DNA polymerase or the entire replication complex. Replication failure by the 40S pathway is known to initiate recombinational events in the damaged SV40 replicons. Similar events in cellular replicons may play a role in the clastogenic effects of formaldehyde. In addition, formaldehyde and acrolein caused accumulation of catenated (topologically linked) SV40 daughter chromosomes--a signature of topoisomerase II inhibition.
Permana
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PA
Department of Radiology, Ohio State University, Columbus 43210.
Snapka
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RM
D000171:Acrolein / Q000494:pharmacology; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002522:Chlorocebus aethiops; D002875:Chromosomes; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000187:drug effects* / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors; D013539:Simian virus 40 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D059005:Topoisomerase II Inhibitors; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
D000447:Aldehydes; D004279:DNA, Viral; D019384:Nucleic Acid Synthesis Inhibitors; D059005:Topoisomerase II Inhibitors; D014764:Viral Proteins; D005557:Formaldehyde; D000171:Acrolein