Structural and dynamic effects of single 7-hydro-8-oxoguanine bases located in a frameshift target DNA sequence
DNA 7-hydro-8-oxoguanine (8-oxoG) is implicated in frameshift formation in an G 6 sequence of the HPRT gene in mismatch repair (MMR) defective cells. Using oligonucleotides based on this frameshift hotspot, we investigated how a single 8-oxoG modified the structural and dynamic properties of the G 6...
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| Veröffentlicht in: | Biophysical chemistry 2005-10, Vol.118 (1), p.31-41 |
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| container_title | Biophysical chemistry |
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| creator | Barone, Flavia Lankas, Filip Spackova, Nada Sponer, Jiri Karran, Peter Bignami, Margherita Mazzei, Filomena |
| description | DNA 7-hydro-8-oxoguanine (8-oxoG) is implicated in frameshift formation in an G
6 sequence of the
HPRT gene in mismatch repair (MMR) defective cells. Using oligonucleotides based on this frameshift hotspot, we investigated how a single 8-oxoG modified the structural and dynamic properties of the G
6 tract. A 30 ns molecular dynamics (MD) simulation indicated compression of the minor groove in the immediate vicinity of the lesion. Fluorescence polarization anisotropy (FPA) and MD demonstrated that 8-oxoG increases DNA torsional rigidity and also constrains the movement of the single-stranded region at the single/double stranded DNA junction of model DNA replication template/primer. These constraints influenced the efficiency of primer extension by Klenow (exo
−) DNA polymerase. |
| doi_str_mv | 10.1016/j.bpc.2005.06.003 |
| format | Article |
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HPRT gene in mismatch repair (MMR) defective cells. Using oligonucleotides based on this frameshift hotspot, we investigated how a single 8-oxoG modified the structural and dynamic properties of the G
6 tract. A 30 ns molecular dynamics (MD) simulation indicated compression of the minor groove in the immediate vicinity of the lesion. Fluorescence polarization anisotropy (FPA) and MD demonstrated that 8-oxoG increases DNA torsional rigidity and also constrains the movement of the single-stranded region at the single/double stranded DNA junction of model DNA replication template/primer. These constraints influenced the efficiency of primer extension by Klenow (exo
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6 sequence of the
HPRT gene in mismatch repair (MMR) defective cells. Using oligonucleotides based on this frameshift hotspot, we investigated how a single 8-oxoG modified the structural and dynamic properties of the G
6 tract. A 30 ns molecular dynamics (MD) simulation indicated compression of the minor groove in the immediate vicinity of the lesion. Fluorescence polarization anisotropy (FPA) and MD demonstrated that 8-oxoG increases DNA torsional rigidity and also constrains the movement of the single-stranded region at the single/double stranded DNA junction of model DNA replication template/primer. These constraints influenced the efficiency of primer extension by Klenow (exo
−) DNA polymerase.</description><subject>7-hydro-8-oxoguanine</subject><subject>Base Pair Mismatch</subject><subject>Base Sequence</subject><subject>DNA - chemistry</subject><subject>DNA conformation</subject><subject>DNA dynamics</subject><subject>DNA Repair</subject><subject>DNA Replication - drug effects</subject><subject>DNA-Directed DNA Polymerase - genetics</subject><subject>DNA-Directed DNA Polymerase - metabolism</subject><subject>Fluorescence Polarization</subject><subject>Frameshift</subject><subject>Guanine - analogs & derivatives</subject><subject>Guanine - chemistry</subject><subject>Guanine - pharmacology</subject><subject>Hypoxanthine Phosphoribosyltransferase - genetics</subject><subject>Molecular dynamics</subject><subject>Nucleic Acid Conformation - drug effects</subject><subject>Templates, Genetic</subject><issn>0301-4622</issn><issn>1873-4200</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEuP0zAUhS0EYkrhB7BBXrFLuLYTOxWr0QwvaQQLYG35cd1xlcTFThD997hqJXZ4cyXrnHPv-Qh5zaBlwOS7Q2uPruUAfQuyBRBPyIYNSjRd_XtKNiCANZ3k_Ia8KOUA9Q0Az8kNkyB2IIYNSd-XvLplzWakZvbUn2YzRUcxBHRLoSnQEuf9iFQ1jyefUzM06U_ar2aOM1JrChY6JmcW9DTO1NCQzYTlMYaFLibvcaH3X29pwV8rzg5fkmfBjAVfXeeW_Pz44cfd5-bh26cvd7cPjRM9WxqrlOXGoaltgLM-2HptD71SwyCVh05xv5NccjF0xjHrOuU4eGt2LKBFIbbk7SX3mFPdXBY9xeJwHM2MaS1aDr0CWf1bwi5Cl1MpGYM-5jiZfNIM9JmyPuhKWZ8pa5C6Uq6eN9fw1U7o_zmuWKvg_UWAteLviFkXF8_1fcwVq_Yp_if-L1DAjQ8</recordid><startdate>20051022</startdate><enddate>20051022</enddate><creator>Barone, Flavia</creator><creator>Lankas, Filip</creator><creator>Spackova, Nada</creator><creator>Sponer, Jiri</creator><creator>Karran, Peter</creator><creator>Bignami, Margherita</creator><creator>Mazzei, Filomena</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20051022</creationdate><title>Structural and dynamic effects of single 7-hydro-8-oxoguanine bases located in a frameshift target DNA sequence</title><author>Barone, Flavia ; Lankas, Filip ; Spackova, Nada ; Sponer, Jiri ; Karran, Peter ; Bignami, Margherita ; Mazzei, Filomena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c351t-b77b2acea8730215fb038505778867d0472d96262384ac1bc47c20dba91febe33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>7-hydro-8-oxoguanine</topic><topic>Base Pair Mismatch</topic><topic>Base Sequence</topic><topic>DNA - chemistry</topic><topic>DNA conformation</topic><topic>DNA dynamics</topic><topic>DNA Repair</topic><topic>DNA Replication - drug effects</topic><topic>DNA-Directed DNA Polymerase - genetics</topic><topic>DNA-Directed DNA Polymerase - metabolism</topic><topic>Fluorescence Polarization</topic><topic>Frameshift</topic><topic>Guanine - analogs & derivatives</topic><topic>Guanine - chemistry</topic><topic>Guanine - pharmacology</topic><topic>Hypoxanthine Phosphoribosyltransferase - genetics</topic><topic>Molecular dynamics</topic><topic>Nucleic Acid Conformation - drug effects</topic><topic>Templates, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barone, Flavia</creatorcontrib><creatorcontrib>Lankas, Filip</creatorcontrib><creatorcontrib>Spackova, Nada</creatorcontrib><creatorcontrib>Sponer, Jiri</creatorcontrib><creatorcontrib>Karran, Peter</creatorcontrib><creatorcontrib>Bignami, Margherita</creatorcontrib><creatorcontrib>Mazzei, Filomena</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biophysical chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barone, Flavia</au><au>Lankas, Filip</au><au>Spackova, Nada</au><au>Sponer, Jiri</au><au>Karran, Peter</au><au>Bignami, Margherita</au><au>Mazzei, Filomena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural and dynamic effects of single 7-hydro-8-oxoguanine bases located in a frameshift target DNA sequence</atitle><jtitle>Biophysical chemistry</jtitle><addtitle>Biophys Chem</addtitle><date>2005-10-22</date><risdate>2005</risdate><volume>118</volume><issue>1</issue><spage>31</spage><epage>41</epage><pages>31-41</pages><issn>0301-4622</issn><eissn>1873-4200</eissn><abstract>DNA 7-hydro-8-oxoguanine (8-oxoG) is implicated in frameshift formation in an G
6 sequence of the
HPRT gene in mismatch repair (MMR) defective cells. Using oligonucleotides based on this frameshift hotspot, we investigated how a single 8-oxoG modified the structural and dynamic properties of the G
6 tract. A 30 ns molecular dynamics (MD) simulation indicated compression of the minor groove in the immediate vicinity of the lesion. Fluorescence polarization anisotropy (FPA) and MD demonstrated that 8-oxoG increases DNA torsional rigidity and also constrains the movement of the single-stranded region at the single/double stranded DNA junction of model DNA replication template/primer. These constraints influenced the efficiency of primer extension by Klenow (exo
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| fulltext | fulltext |
| identifier | ISSN: 0301-4622 |
| ispartof | Biophysical chemistry, 2005-10, Vol.118 (1), p.31-41 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 7-hydro-8-oxoguanine Base Pair Mismatch Base Sequence DNA - chemistry DNA conformation DNA dynamics DNA Repair DNA Replication - drug effects DNA-Directed DNA Polymerase - genetics DNA-Directed DNA Polymerase - metabolism Fluorescence Polarization Frameshift Guanine - analogs & derivatives Guanine - chemistry Guanine - pharmacology Hypoxanthine Phosphoribosyltransferase - genetics Molecular dynamics Nucleic Acid Conformation - drug effects Templates, Genetic |
| title | Structural and dynamic effects of single 7-hydro-8-oxoguanine bases located in a frameshift target DNA sequence |
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