Solution structure of the single-strand break repair protein XRCC1 N-terminal domain
XRCC1 functions in the repair of single-strand DNA breaks in mammalian cells and forms a repair complex with β-Pol, ligase III and PARP. Here we describe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD). The structural core is a β-sandwich with β-strands connected by loops, thre...
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| Veröffentlicht in: | Nature Structural Biology 1999-09, Vol.6 (9), p.884-893 |
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| creator | Marintchev, Assen Mullen, Mary A. Maciejewski, Mark W. Pan, Borlan Gryk, Michael R. Mullen, Gregory P. |
| description | XRCC1 functions in the repair of single-strand DNA breaks in mammalian cells and forms a repair complex with β-Pol, ligase III and PARP. Here we describe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD). The structural core is a β-sandwich with β-strands connected by loops, three helices and two short two-stranded β-sheets at each connection side. We show, for the first time, that the XRCC1 NTD specifically binds single-strand break DNA (gapped and nicked). We also show that the XRCC1 NTD binds a gapped DNA–β-Pol complex. The DNA binding and β-Pol binding surfaces were mapped by NMR and found to be well suited for interaction with single-strand gap DNA containing a 90° bend, and for simultaneously making contacts with the palm-thumb of β-Pol in a ternary complex. The findings suggest a mechanism for preferential binding of the XRCC1 NTD to flexible single-strand break DNA. |
| doi_str_mv | 10.1038/12347 |
| format | Article |
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Here we describe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD). The structural core is a β-sandwich with β-strands connected by loops, three helices and two short two-stranded β-sheets at each connection side. We show, for the first time, that the XRCC1 NTD specifically binds single-strand break DNA (gapped and nicked). We also show that the XRCC1 NTD binds a gapped DNA–β-Pol complex. The DNA binding and β-Pol binding surfaces were mapped by NMR and found to be well suited for interaction with single-strand gap DNA containing a 90° bend, and for simultaneously making contacts with the palm-thumb of β-Pol in a ternary complex. 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Here we describe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD). The structural core is a β-sandwich with β-strands connected by loops, three helices and two short two-stranded β-sheets at each connection side. We show, for the first time, that the XRCC1 NTD specifically binds single-strand break DNA (gapped and nicked). We also show that the XRCC1 NTD binds a gapped DNA–β-Pol complex. The DNA binding and β-Pol binding surfaces were mapped by NMR and found to be well suited for interaction with single-strand gap DNA containing a 90° bend, and for simultaneously making contacts with the palm-thumb of β-Pol in a ternary complex. The findings suggest a mechanism for preferential binding of the XRCC1 NTD to flexible single-strand break DNA.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Biochemistry</subject><subject>Biological Microscopy</subject><subject>Biomedical and Life Sciences</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA Damage - genetics</subject><subject>DNA Polymerase beta - metabolism</subject><subject>DNA Repair - genetics</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Evolution, Molecular</subject><subject>Glutamic Acid - genetics</subject><subject>Glutamic Acid - metabolism</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Membrane Biology</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Pliability</subject><subject>Protein Binding</subject><subject>Protein Structure</subject><subject>Protein Structure, Secondary</subject><subject>Sequence Alignment</subject><subject>solution structure</subject><subject>Solutions</subject><subject>Space life sciences</subject><subject>Thermodynamics</subject><subject>X-ray Repair Cross Complementing Protein 1</subject><subject>XRCC1 protein</subject><issn>1072-8368</issn><issn>1545-9985</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctOwzAQtBCIltJfQD5xC9hx_DqiiJdUgQQ9cIvsxC4uiVNs58DfY6CII6cd7c6MdncAWGJ0gRERl7gkFT8Ac0wrWkgp6GHGiJeFIEzMwEmMW4RKSjk5BjOMKsYxKudg_Tz2U3KjhzGFqU1TMHC0ML0aGJ3f9KbIfeU7qINRbzCYnXIB7sKYjPPw5amuMXwokgmD86qH3Tgo50_BkVV9NMt9XYD1zfW6vitWj7f39dWqaAmiqdAGyZYLooW2trJEcNOZDLXuRIsl5wQTjSVVreisQpRRK7C0LKuzSpAFOP-xzeu8TyamZnCxNX2vvBmn2DApJStZ-S8Rc8okwzQTz_bESQ-ma3bBDSp8NL__-nOKeeQ3JjTbcQr58myCmq8gmu8gyCc5KXdj</recordid><startdate>19990901</startdate><enddate>19990901</enddate><creator>Marintchev, Assen</creator><creator>Mullen, Mary A.</creator><creator>Maciejewski, Mark W.</creator><creator>Pan, Borlan</creator><creator>Gryk, Michael R.</creator><creator>Mullen, Gregory P.</creator><general>Nature Publishing Group US</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>19990901</creationdate><title>Solution structure of the single-strand break repair protein XRCC1 N-terminal domain</title><author>Marintchev, Assen ; 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Here we describe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD). The structural core is a β-sandwich with β-strands connected by loops, three helices and two short two-stranded β-sheets at each connection side. We show, for the first time, that the XRCC1 NTD specifically binds single-strand break DNA (gapped and nicked). We also show that the XRCC1 NTD binds a gapped DNA–β-Pol complex. The DNA binding and β-Pol binding surfaces were mapped by NMR and found to be well suited for interaction with single-strand gap DNA containing a 90° bend, and for simultaneously making contacts with the palm-thumb of β-Pol in a ternary complex. The findings suggest a mechanism for preferential binding of the XRCC1 NTD to flexible single-strand break DNA.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>10467102</pmid><doi>10.1038/12347</doi><tpages>10</tpages></addata></record> |
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| subjects | Amino Acid Sequence Animals Binding Sites Biochemistry Biological Microscopy Biomedical and Life Sciences DNA - genetics DNA - metabolism DNA Damage - genetics DNA Polymerase beta - metabolism DNA Repair - genetics DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism Evolution, Molecular Glutamic Acid - genetics Glutamic Acid - metabolism Humans Life Sciences Membrane Biology Models, Molecular Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Pliability Protein Binding Protein Structure Protein Structure, Secondary Sequence Alignment solution structure Solutions Space life sciences Thermodynamics X-ray Repair Cross Complementing Protein 1 XRCC1 protein |
| title | Solution structure of the single-strand break repair protein XRCC1 N-terminal domain |
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