Mechanism of nonhomologous end-joining in mycobacteria: A low-fidelity repair system driven by Ku, ligase D and ligase C Journal Article
| Authors: | Gong, C.; Bongiorno, P.; Martins, A.; Stephanou, N. C.; Zhu, H.; Shuman, S.; Glickman, M. S. |
| Article Title: | Mechanism of nonhomologous end-joining in mycobacteria: A low-fidelity repair system driven by Ku, ligase D and ligase C |
| Abstract: | DNA double-strand breaks (DSBs) can be repaired either via homologous recombination (HR) or nonhomologous end-joining (NHEJ). Both pathways are operative in eukaryotes, but bacteria had been thought to rely on HR alone. Here we provide direct evidence that mycobacteria have a robust NHEJ pathway that requires Ku and a specialized polyfunctional ATP-dependent DNA ligase (LigD). NHEJ of blunt-end and complementary 5′-overhang DSBs is highly mutagenic (∼50% error rate). Analysis of the recombination junctions ensuing from individual NHEJ events highlighted the participation of several DNA end-remodeling activities, including template-dependent fill-in of 5′ overhangs, nontemplated addition of single nucleotides at blunt ends, and nucleolytic resection. LigD itself has the template-dependent and template-independent polymerase functions in vitro that compose the molecular signatures of NHEJ in vivo. Another ATP-dependent DNA ligase (LigC) provides a backup mechanism for LigD-independent error-prone repair of blunt-end DSBs. We speculate that NHEJ allows mycobacteria to evade genotoxic host defense. |
| Keywords: | signal transduction; dna binding protein; sequence analysis; genetics; mutation; dna-binding proteins; nonhuman; genetic analysis; protein analysis; phenotype; metabolism; dna damage; dna repair; protein binding; enzyme activity; bacterial strain; bacteria (microorganisms); dna strand breakage; bacterial protein; chemistry; bacterial proteins; dna; genetic recombination; eukaryota; recombination, genetic; nucleotide sequence; base sequence; ku antigen; polydeoxyribonucleotide synthase; mycobacterium; corynebacterineae; dna ligases; mycobacterium smegmatis; open reading frame; dna template; antigens, nuclear; templates, genetic; microbial activity; mutagenic activity; cell nucleus antigen; polydeoxyribonucleotide synthase (atp) |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 12 |
| Issue: | 4 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-04-01 |
| Start Page: | 304 |
| End Page: | 312 |
| Language: | English |
| DOI: | 10.1038/nsmb915 |
| PROVIDER: | scopus |
| PUBMED: | 15778718 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 62" - "Export Date: 24 October 2012" - "CODEN: NSMBC" - "Source: Scopus" |
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