Bacterial nonhomologous end joining ligases preferentially seal breaks with a 3′-OH monoribonucleotide Journal Article
| Authors: | Zhu, H.; Shuman, S. |
| Article Title: | Bacterial nonhomologous end joining ligases preferentially seal breaks with a 3′-OH monoribonucleotide |
| Abstract: | Many bacterial species have a nonhomologous end joining system of DNA repair driven by dedicated DNA ligases (LigD and LigC). LigD is a multifunctional enzyme composed of a ligase domain fused to two other catalytic modules: a polymerase that preferentially adds ribonucleotides to double-strand break ends and a phosphoesterase that trims 3′-oligoribonucleotide tracts until only a single 3′-ribonucleotide remains. LigD and LigC have a feeble capacity to seal 3′-OH/5′-PO4 DNA nicks. Here, we report that nick sealing by LigD and LigC enzymes is stimulated by the presence of a single ribonucleotide at the broken 3′-OH end. The ribonucleotide effect on LigD and LigC is specific for the 3′-terminal nucleotide and is either diminished or abolished when additional vicinal ribonucleotides are present. No such 3′-ribonucleotide effect is observed for bacterial LigA or Chlorella virus ligase. We found that in vitro repair of a double-strand break by Pseudomonas LigD requires the polymerase module and results in incorporation of an alkali-labile ribonucleotide at the repair junction. These results illuminate an underlying logic for the domain organization of LigD, whereby the polymerase and phosphoesterase domains can heal the broken 3′-end to generate the monoribonucleotide terminus favored by the nonhomologous end joining ligases. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | controlled study; unclassified drug; genetics; nonhuman; molecular genetics; protein domain; metabolism; dna damage; dna repair; genes; phosphatase; enzymology; bacteria (microorganisms); dna strand breakage; dna; double stranded dna; molecular sequence data; kinetics; nucleotide sequence; nucleic acids; substrate specificity; dna breaks, double-stranded; double stranded dna break; base sequence; organic acids; polydeoxyribonucleotide synthase; enzyme specificity; enzymes; repair; in vitro; chlorella virus; dna ligases; ligase; ligases; liga; maintenance; ribonucleotide; pseudomonas aeruginosa; polymers; bacteriology; dna ligase d; pseudomonas; ribonucleotides; joining; bacterial species; do-mains; dna repairs; strand breaks; catalytic modules; domain organizations; multi-functional; dna ligase c; nonhomologous end joining ligase; chlorella |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 283 |
| Issue: | 13 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2008-03-28 |
| Start Page: | 8331 |
| End Page: | 8339 |
| Language: | English |
| DOI: | 10.1074/jbc.M705476200 |
| PUBMED: | 18203718 |
| PROVIDER: | scopus |
| PMCID: | PMC2276377 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: JBCHA" - "Source: Scopus" |
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