PMID:21491964
| Citation |
Jasti, VP, Das, RS, Hilton, BA, Weerasooriya, S, Zou, Y and Basu, AK (2011) (5'S)-8,5'-cyclo-2'-deoxyguanosine is a strong block to replication, a potent pol V-dependent mutagenic lesion, and is inefficiently repaired in Escherichia coli. Biochemistry 50:3862-5 |
|---|---|
| Abstract |
8,5'-Cyclopurines, making up an important class of ionizing radiation-induced tandem DNA damage, are repaired only by nucleotide excision repair (NER). They accumulate in NER-impaired cells, as in Cockayne syndrome group B and certain Xeroderma Pigmentosum patients. A plasmid containing (5'S)-8,5'-cyclo-2'-deoxyguanosine (S-cdG) was replicated in Escherichia coli with specific DNA polymerase knockouts. Viability was <1% in the wild-type strain, which increased to 5.5% with SOS. Viability decreased further in a pol II(-) strain, whereas it increased considerably in a pol IV(-) strain. Remarkably, no progeny was recovered from a pol V(-) strain, indicating that pol V is absolutely required for bypassing S-cdG. Progeny analyses indicated that S-cdG is significantly mutagenic, inducing ~34% mutation with SOS. Most mutations were S-cdG → A mutations, though S-cdG → T mutation and deletion of 5'C also occurred. Incisions of purified UvrABC nuclease on S-cdG, S-cdA, and C8-dG-AP on a duplex 51-mer showed that the incision rates are C8-dG-AP > S-cdA > S-cdG. In summary, S-cdG is a major block to DNA replication, highly mutagenic, and repaired slowly in E. coli. |
| Links |
PubMed PMC3092667 Online version:10.1021/bi2004944 |
| Keywords |
DNA Repair/drug effects; DNA Repair/genetics; DNA Repair/radiation effects; DNA Replication/drug effects; DNA Replication/genetics; DNA Replication/radiation effects; DNA-Directed RNA Polymerases/antagonists & inhibitors; DNA-Directed RNA Polymerases/chemistry; DNA-Directed RNA Polymerases/genetics; Deoxyguanosine/analogs & derivatives; Deoxyguanosine/chemistry; Deoxyguanosine/genetics; Deoxyguanosine/toxicity; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/radiation effects; Mutagenesis/drug effects; Mutagenesis/genetics; Mutagenesis/radiation effects; SOS Response (Genetics)/drug effects; SOS Response (Genetics)/genetics; SOS Response (Genetics)/radiation effects |
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