Effects of 3'-OH and 5'-PO4 base mispairs and damaged base lesions on the fidelity of nick sealing by Deinococcus radiodurans RNA ligase Journal Article
| Authors: | Schmier, B. J.; Shuman, S. |
| Article Title: | Effects of 3'-OH and 5'-PO4 base mispairs and damaged base lesions on the fidelity of nick sealing by Deinococcus radiodurans RNA ligase |
| Abstract: | Deinococcus radiodurans RNA ligase (DraRnl) is the founding member of a family of end-joining enzymes encoded by diverse microbes and viruses. DraRnl ligates 3'-OH, 5'-PO4 nicks in double-stranded nucleic acids in which the nick 3'-OH end is RNA. Here we gauge the effects of 3'-OH and 5'-PO4 base mispairs and damaged base lesions on the rate of nick sealing. DraRnl is indifferent to the identity of the 3'-OH nucleobase, provided that it is correctly paired. With 3'-OH mispairs, the DraRnl sealing rate varies widely, with G-T and A-C mispairs being the best substrates and G-G, G-A, and A-A mispairs being the worst. DraRnl accepts 3' A-8-oxoguanine (oxoG) to be correctly paired, while it discriminates against U-oxoG and G-oxoG mispairs. DraRnl displays high activity and low fidelity in sealing 3'-OH ends opposite an 8-oxoadenine lesion. It prefers 3'-OH adenosine when sealing opposite an abasic template site. With 5'-PO4 mispairs, DraRnl seals a 5' T-G mispair as well as it does a 5' C-G pair; in most other respects, the ligation fidelity at 5' mispairs is similar to that at 3' mispairs. DraRnl accepts a 5' A-oxoG end to be correctly paired, yet it is more tolerant of 5' T-oxoG and 5' G-oxoG mispairs than the equivalent configurations on the 3' side of the nick. At 5' nucleobase-abasic site nicks, DraRnl prefers to ligate when the nucleobase is a purine. The biochemical properties of DraRnl are compatible with its participation in the templated repair of RNA damage or in the sealing of filled DNA gaps that have a 3' ribopatch. © 2014, American Society for Microbiology. |
| Keywords: | nonhuman; dna damage; adenosine; rna structure; polydeoxyribonucleotide synthase; phosphate; pyrimidine; polyacrylamide gel electrophoresis; nucleotide; 8 hydroxyguanine; rna polymerase; purine; dna rna hybridization; dna template; dna strand; deinococcus radiodurans; rna ligase; edetic acid; rna editing; nucleic acid base; priority journal; article; formamide |
| Journal Title: | Journal of Bacteriology |
| Volume: | 196 |
| Issue: | 9 |
| ISSN: | 0021-9193 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2014-05-01 |
| Start Page: | 1704 |
| End Page: | 1712 |
| Language: | English |
| DOI: | 10.1128/jb.00020-14 |
| PROVIDER: | scopus |
| PUBMED: | 24532777 |
| PMCID: | PMC3993322 |
| DOI/URL: | |
| Notes: | Export Date: 1 May 2014 -- CODEN: JOBAA -- Source: Scopus |
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