Rewriting the rules for end joining via enzymatic splicing of DNA 3′-PO4 and 5′-OH ends Journal Article
| Authors: | Das, U.; Chakravarty, A. K.; Remus, B. S.; Shuman, S. |
| Article Title: | Rewriting the rules for end joining via enzymatic splicing of DNA 3′-PO4 and 5′-OH ends |
| Abstract: | There are many biological contexts in which DNA damage generates "dirty" breaks with 3′-PO4 (or cyclic-PO4) and 5′-OH ends that cannot be sealed by DNA ligases. Here we show that the Escherichia coli RNA ligase RtcB can splice these dirty DNA ends via a unique chemical mechanism. RtcB transfers GMP from a covalent RtcB.GMP intermediate to a DNA 3′-PO4 to form a "capped" 3′ end structure, DNA3′-5′G. When a suitable DNA 5′-OH end is available, RtcB catalyzes attack of the 5′-OH on DNA3′-5′G to form a 3′.5′ phosphodiester splice junction. Our findings unveil an enzymatic capacity for DNA 3′ capping and the sealing of DNA breaks with 3′-PO4 and 5′-OH termini, with implications for DNA repair and DNA rearrangements. |
| Keywords: | controlled study; unclassified drug; protein function; enzyme activity; dna structure; catalysis; enzyme mechanism; dna splicing; rna ligase; guanosine phosphate; dna end joining repair; priority journal; article; rna ligase rtcb; enzymatic dna splicing |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 110 |
| Issue: | 51 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2013-12-17 |
| Start Page: | 20437 |
| End Page: | 20442 |
| Language: | English |
| DOI: | 10.1073/pnas.1314289110 |
| PROVIDER: | scopus |
| PMCID: | PMC3870732 |
| PUBMED: | 24218597 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):1 -- Export Date: 3 February 2014 -- CODEN: PNASA -- Source: Scopus |
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