Structure of a NHEJ Polymerase-Mediated DNA Synaptic Complex
Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). Th...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2007-10, Vol.318 (5849), p.456-459 |
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| creator | Brissett, Nigel C. Pitcher, Robert S. Juarez, Raquel Picher, Angel J. Green, Andrew J. Dafforn, Timothy R. Fox, Gavin C. Blanco, Luis Doherty, Aidan J. |
| description | Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of Mycobacterium tuberculosis polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3′ termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining. |
| doi_str_mv | 10.1126/science.1145112 |
| format | Article |
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Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of Mycobacterium tuberculosis polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3′ termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1145112</identifier><identifier>PMID: 17947582</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Amino Acid Sequence ; Base Sequence ; Biological and medical sciences ; Crystal structure ; Crystallography, X-Ray ; Deoxyribonucleic acid ; Dimerization ; DNA ; DNA Ligases - chemistry ; DNA Ligases - genetics ; DNA Ligases - metabolism ; DNA Repair ; DNA, Bacterial - chemistry ; DNA, Bacterial - metabolism ; Fluorescence ; Fundamental and applied biological sciences. Psychology ; General aspects. Models. Methods ; Genomics ; Grants ; Models, Molecular ; Molecular Sequence Data ; Molecules ; Monomers ; Mutation ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - chemistry ; Mycobacterium tuberculosis - enzymology ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - metabolism ; Nucleic acids ; Nucleotides ; Protein Conformation ; Protein Structure, Tertiary ; Proteins ; Research facilities ; Research grants ; Signal transduction ; Vertebrates: nervous system and sense organs</subject><ispartof>Science (American Association for the Advancement of Science), 2007-10, Vol.318 (5849), p.456-459</ispartof><rights>Copyright 2007 American Association for the Advancement of Science</rights><rights>2008 INIST-CNRS</rights><rights>Copyright © 2007, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-c44ddb7f50c553c16c7451e069eb45aba67b491cb132aa757d57b86848a3747c3</citedby><cites>FETCH-LOGICAL-c435t-c44ddb7f50c553c16c7451e069eb45aba67b491cb132aa757d57b86848a3747c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20051405$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20051405$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2870,2871,27903,27904,57996,58229</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19193779$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17947582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brissett, Nigel C.</creatorcontrib><creatorcontrib>Pitcher, Robert S.</creatorcontrib><creatorcontrib>Juarez, Raquel</creatorcontrib><creatorcontrib>Picher, Angel J.</creatorcontrib><creatorcontrib>Green, Andrew J.</creatorcontrib><creatorcontrib>Dafforn, Timothy R.</creatorcontrib><creatorcontrib>Fox, Gavin C.</creatorcontrib><creatorcontrib>Blanco, Luis</creatorcontrib><creatorcontrib>Doherty, Aidan J.</creatorcontrib><title>Structure of a NHEJ Polymerase-Mediated DNA Synaptic Complex</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of Mycobacterium tuberculosis polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3′ termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining.</description><subject>Amino Acid Sequence</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Deoxyribonucleic acid</subject><subject>Dimerization</subject><subject>DNA</subject><subject>DNA Ligases - chemistry</subject><subject>DNA Ligases - genetics</subject><subject>DNA Ligases - metabolism</subject><subject>DNA Repair</subject><subject>DNA, Bacterial - chemistry</subject><subject>DNA, Bacterial - metabolism</subject><subject>Fluorescence</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects. Models. 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Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of Mycobacterium tuberculosis polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3′ termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>17947582</pmid><doi>10.1126/science.1145112</doi><tpages>4</tpages></addata></record> |
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| subjects | Amino Acid Sequence Base Sequence Biological and medical sciences Crystal structure Crystallography, X-Ray Deoxyribonucleic acid Dimerization DNA DNA Ligases - chemistry DNA Ligases - genetics DNA Ligases - metabolism DNA Repair DNA, Bacterial - chemistry DNA, Bacterial - metabolism Fluorescence Fundamental and applied biological sciences. Psychology General aspects. Models. Methods Genomics Grants Models, Molecular Molecular Sequence Data Molecules Monomers Mutation Mycobacterium tuberculosis Mycobacterium tuberculosis - chemistry Mycobacterium tuberculosis - enzymology Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - metabolism Nucleic acids Nucleotides Protein Conformation Protein Structure, Tertiary Proteins Research facilities Research grants Signal transduction Vertebrates: nervous system and sense organs |
| title | Structure of a NHEJ Polymerase-Mediated DNA Synaptic Complex |
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