Escherichia coli RecA promotes strand invasion with cisplatin-damaged DNA.
The antitumor drug cisplatin causes intrastrand cross-linking of adjacent guanine residues that severely distorts the DNA backbone. These DNA adducts impede the progress of the replisome and may result in replication fork arrest. In Escherichia coli, the response to cisplatin involves the action of the prototypic recombinase RecA. Here we show that RecA can utilize, albeit at reduced levels, oligonucleotides that bear site-specific cisplatin-induced 1,2 d(GpG) intrastrand cross-links in strand invasion reactions. Binding of RecA to cisplatin-damaged oligonucleotides was not affected, indicating that the impediment was in the pairing step. The cognate E. coli single-strand DNA-binding protein specifically stimulated strand invasion particularly with cisplatin-damaged DNA. These results indicate that RecA is capable of processing the major cisplatin-induced lesion via a recombination mechanism.
Nimonkar
A V
AV
Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, P.O. Box 016129, FL 33101-6129, USA.
Le Gac
N Tanguy
NT
Villani
G
G
Boehmer
P E
PE
D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D018736:DNA Adducts / Q000235:genetics / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000502:physiology; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011938:Rec A Recombinases / Q000502:physiology*; D011995:Recombination, Genetic / Q000187:drug effects; D013997:Time Factors
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; D029968:Escherichia coli Proteins; C476430:SSB protein, E coli; C034298:deoxyguanylyl-(3'-5')-guanosine; D011938:Rec A Recombinases; D002945:Cisplatin