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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chauleau, Mathieu Das, Ushati Shuman, Stewart Ordonez, Heather |
| Description | Author Affiliation: Das U ( Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065.); Chauleau M ( Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065.); Ordonez H ( Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065.); Shuman S ( Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065 s-shuman@ski.mskcc.org.); |
| Abstract | Many biological scenarios generate 'dirty' DNA 3'-PO4 ends that cannot be sealed by classic DNA ligases or extended by DNA polymerases. The noncanonical ligase RtcB can 'cap' these ends via a unique chemical mechanism entailing transfer of GMP from a covalent RtcB-GMP intermediate to a DNA 3'-PO4 to form DNA3'pp5'G. Here, we show that capping protects DNA 3' ends from resection by Escherichia coli exonucleases I and III and from end-healing by T4 polynucleotide 3' phosphatase. By contrast, the cap is an effective primer for DNA synthesis. E. coli DNA polymerase I and Mycobacterium DinB1 extend the DNAppG primer to form an alkali-labile DNApp(rG)pDNA product. The addition of dNTP depends on pairing of the cap guanine with an opposing cytosine in the template strand. Aprataxin, an enzyme implicated in repair of A5'pp5'DNA ends formed during abortive ligation by classic ligases, is highly effective as a DNA 3' decapping enzyme, converting DNAppG to DNA3'p and GMP. We conclude that the biochemical impact of DNA capping is to prevent resection and healing of a 3'-PO4 end, while permitting DNA synthesis, at the price of embedding a ribonucleotide and a pyrophosphate linkage in the repaired strand. Aprataxin affords a means to counter the impact of DNA capping. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 31 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Repair DNA Metabolism Guanosine RNA Caps Biosynthesis DNA-Directed DNA Polymerase Escherichia Coli Enzymology Exodeoxyribonucleases Exonucleases Molecular Sequence Data Nucleotides Phosphoprotein Phosphatases Schizosaccharomyces Pombe Proteins Templates, Genetic Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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