ALDEHYDE-INDUCED PROTEIN - DNA CROSS-LINKS DISRUPT SPECIFIC STAGES OFSV40 DNA-REPLICATION

Aldehydes with specific protein-DNA crosslinking ability disrupted sim ian virus 40 (SV40) DNA replication to cause replication fork failure by the 40S intermediate pathway, in which replicating viral genomes be come inactivated and torsionally stressed. In contrast, aldehydes with out detectable protein-DNA crosslinking ability had no effect on SV40 DNA replication during the 10 min exposure times employed. This indica tes that protein-DNA crosslinks block either DNA polymerase or the ent ire replication complex. Replication failure by the 405 pathway is kno wn to initiate recombinational events in the damaged SV40 replicons. S imilar events in cellular replicons may play a role in the clastogenic effects of formaldehyde. In addition, formaldehyde acid acrolein caus ed accumulation of catenated (topologically linked) SV40 daughter chro mosomes-a signature of topoisomerase II inhibition.