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© 1994 Oxford University Press

other

Aldehyde-induced protein—DNA crosslinks disrupt specific stages of SV4I) DNA replication

Paskasari A. Permana 1 and Robert M. Snapka 2

Departments of Radiology and Medical Microbiology and Immunology, The Otio State University Columbus, OH 43210, USA

2whom reprint requests should be sent

Aldehydes with specific protein-DNA crosslinking ability disrupted simian virus 40 (SV4O) 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 crosslinldng ability had no effect on SV4O 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 SV4O replicons. Similar events in cellular repilcons may play a role in the clastogenic effects of formaldehyde. In addition, formaldehyde and acrolein caused accumulation of catenated (topologically linked) SV4O daughter chromosomes—a signature of topoisomerase II inhibition.


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