Low‐Energy Electron‐Induced Strand Breaks in Telomere‐Derived DNA Sequences—Influence of DNA Sequence and Topology
During cancer radiation therapy high‐energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low‐energy (
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| Veröffentlicht in: | Chemistry : a European journal 2018-03, Vol.24 (18), p.4680-4688 |
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| creator | Rackwitz, Jenny Bald, Ilko |
| description | During cancer radiation therapy high‐energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low‐energy ( |
| doi_str_mv | 10.1002/chem.201705889 |
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Folding for a cause: Telomeric DNA is guanine‐rich and particularly sensitive to low‐energy electrons. By using DNA origami templates, electron (8.8 eV) induced strand breaks are systematically quantified for different sequences, telomere lengths and folding states (G‐quadruplex vs. open form). Accordingly, the strand breakage is more effective in sequences with A adjacent to G, in longer sequences and in a non‐folded state. The present results could be exploited in cancer radiation therapy.</description><identifier>ISSN: 0947-6539</identifier><identifier>EISSN: 1521-3765</identifier><identifier>DOI: 10.1002/chem.201705889</identifier><identifier>PMID: 29359819</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Breakage ; Cancer ; Chemistry ; Cross-sections ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA strand breaks ; Electron attachment ; Electrons ; Energy ; Gene sequencing ; Intermediates ; Irradiation ; low-energy electron ; Nucleotide sequence ; Radiation ; Radiation therapy ; telomeric DNA ; Topology ; Tumors</subject><ispartof>Chemistry : a European journal, 2018-03, Vol.24 (18), p.4680-4688</ispartof><rights>2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3259-8a5ce9c59c67a8368b127c4007afef2167dcdcb6abcf5df546cf42ab97a7e1a23</citedby><cites>FETCH-LOGICAL-c3259-8a5ce9c59c67a8368b127c4007afef2167dcdcb6abcf5df546cf42ab97a7e1a23</cites><orcidid>0000-0002-6683-5065</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fchem.201705889$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fchem.201705889$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29359819$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rackwitz, Jenny</creatorcontrib><creatorcontrib>Bald, Ilko</creatorcontrib><title>Low‐Energy Electron‐Induced Strand Breaks in Telomere‐Derived DNA Sequences—Influence of DNA Sequence and Topology</title><title>Chemistry : a European journal</title><addtitle>Chemistry</addtitle><description>During cancer radiation therapy high‐energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low‐energy (<20 eV) electrons, which are able to damage DNA very efficiently by dissociative electron attachment. Recently, it was suggested that low‐energy electron‐induced DNA strand breaks strongly depend on the specific DNA sequence with a high sensitivity of G‐rich sequences. Here, we use DNA origami platforms to expose G‐rich telomere sequences to low‐energy (8.8 eV) electrons to determine absolute cross sections for strand breakage and to study the influence of sequence modifications and topology of telomeric DNA on the strand breakage. We find that the telomeric DNA 5′‐(TTA GGG)2 is more sensitive to low‐energy electrons than an intermixed sequence 5′‐(TGT GTG A)2 confirming the unique electronic properties resulting from G‐stacking. With increasing length of the oligonucleotide (i.e., going from 5′‐(GGG ATT)2 to 5′‐(GGG ATT)4), both the variety of topology and the electron‐induced strand break cross sections increase. Addition of K+ ions decreases the strand break cross section for all sequences that are able to fold G‐quadruplexes or G‐intermediates, whereas the strand break cross section for the intermixed sequence remains unchanged. These results indicate that telomeric DNA is rather sensitive towards low‐energy electron‐induced strand breakage suggesting significant telomere shortening that can also occur during cancer radiation therapy.
Folding for a cause: Telomeric DNA is guanine‐rich and particularly sensitive to low‐energy electrons. By using DNA origami templates, electron (8.8 eV) induced strand breaks are systematically quantified for different sequences, telomere lengths and folding states (G‐quadruplex vs. open form). Accordingly, the strand breakage is more effective in sequences with A adjacent to G, in longer sequences and in a non‐folded state. The present results could be exploited in cancer radiation therapy.</description><subject>Breakage</subject><subject>Cancer</subject><subject>Chemistry</subject><subject>Cross-sections</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA strand breaks</subject><subject>Electron attachment</subject><subject>Electrons</subject><subject>Energy</subject><subject>Gene sequencing</subject><subject>Intermediates</subject><subject>Irradiation</subject><subject>low-energy electron</subject><subject>Nucleotide sequence</subject><subject>Radiation</subject><subject>Radiation therapy</subject><subject>telomeric DNA</subject><subject>Topology</subject><subject>Tumors</subject><issn>0947-6539</issn><issn>1521-3765</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkc1uEzEURi0EoqFlyxKNxKabCf4Zj-1lSQONFMqiYW15PNdlyowd7AxVWPURWPCEfRIc0hbBpqsrXx8fffKH0CuCpwRj-tZ-gWFKMRGYS6meoAnhlJRM1PwpmmBVibLmTB2gFyldYYxVzdhzdEAV40oSNUE_luH69ubn3EO83BbzHuwmBp83C9-OFtriYhONb4t3EczXVHS-WEEfBoiQmVOI3ffMnJ6fFBfwbQRvId3e_Fp41_85FMH9c1nsVKuwDn243B6hZ870CV7ezUP0-f18NTsrl58-LGYny9IyylUpDbegLFe2FkayWjaEClthLIwDR0ktWtvapjaNdbx1vKqtq6hplDACiKHsEB3vvesYcoy00UOXLPS98RDGpIlSuJKcM5nRN_-hV2GMPqfTuz9WjEjOMjXdUzaGlCI4vY7dYOJWE6x3rehdK_qhlfzg9Z12bAZoH_D7GjKg9sB118P2EZ2enc0__pX_BquvndI</recordid><startdate>20180326</startdate><enddate>20180326</enddate><creator>Rackwitz, Jenny</creator><creator>Bald, Ilko</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6683-5065</orcidid></search><sort><creationdate>20180326</creationdate><title>Low‐Energy Electron‐Induced Strand Breaks in Telomere‐Derived DNA Sequences—Influence of DNA Sequence and Topology</title><author>Rackwitz, Jenny ; Bald, Ilko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3259-8a5ce9c59c67a8368b127c4007afef2167dcdcb6abcf5df546cf42ab97a7e1a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Breakage</topic><topic>Cancer</topic><topic>Chemistry</topic><topic>Cross-sections</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA strand breaks</topic><topic>Electron attachment</topic><topic>Electrons</topic><topic>Energy</topic><topic>Gene sequencing</topic><topic>Intermediates</topic><topic>Irradiation</topic><topic>low-energy electron</topic><topic>Nucleotide sequence</topic><topic>Radiation</topic><topic>Radiation therapy</topic><topic>telomeric DNA</topic><topic>Topology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rackwitz, Jenny</creatorcontrib><creatorcontrib>Bald, Ilko</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry : a European journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rackwitz, Jenny</au><au>Bald, Ilko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low‐Energy Electron‐Induced Strand Breaks in Telomere‐Derived DNA Sequences—Influence of DNA Sequence and Topology</atitle><jtitle>Chemistry : a European journal</jtitle><addtitle>Chemistry</addtitle><date>2018-03-26</date><risdate>2018</risdate><volume>24</volume><issue>18</issue><spage>4680</spage><epage>4688</epage><pages>4680-4688</pages><issn>0947-6539</issn><eissn>1521-3765</eissn><abstract>During cancer radiation therapy high‐energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low‐energy (<20 eV) electrons, which are able to damage DNA very efficiently by dissociative electron attachment. Recently, it was suggested that low‐energy electron‐induced DNA strand breaks strongly depend on the specific DNA sequence with a high sensitivity of G‐rich sequences. Here, we use DNA origami platforms to expose G‐rich telomere sequences to low‐energy (8.8 eV) electrons to determine absolute cross sections for strand breakage and to study the influence of sequence modifications and topology of telomeric DNA on the strand breakage. We find that the telomeric DNA 5′‐(TTA GGG)2 is more sensitive to low‐energy electrons than an intermixed sequence 5′‐(TGT GTG A)2 confirming the unique electronic properties resulting from G‐stacking. With increasing length of the oligonucleotide (i.e., going from 5′‐(GGG ATT)2 to 5′‐(GGG ATT)4), both the variety of topology and the electron‐induced strand break cross sections increase. Addition of K+ ions decreases the strand break cross section for all sequences that are able to fold G‐quadruplexes or G‐intermediates, whereas the strand break cross section for the intermixed sequence remains unchanged. These results indicate that telomeric DNA is rather sensitive towards low‐energy electron‐induced strand breakage suggesting significant telomere shortening that can also occur during cancer radiation therapy.
Folding for a cause: Telomeric DNA is guanine‐rich and particularly sensitive to low‐energy electrons. By using DNA origami templates, electron (8.8 eV) induced strand breaks are systematically quantified for different sequences, telomere lengths and folding states (G‐quadruplex vs. open form). Accordingly, the strand breakage is more effective in sequences with A adjacent to G, in longer sequences and in a non‐folded state. The present results could be exploited in cancer radiation therapy.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29359819</pmid><doi>10.1002/chem.201705889</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6683-5065</orcidid></addata></record> |
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| subjects | Breakage Cancer Chemistry Cross-sections Deoxyribonucleic acid DNA DNA damage DNA strand breaks Electron attachment Electrons Energy Gene sequencing Intermediates Irradiation low-energy electron Nucleotide sequence Radiation Radiation therapy telomeric DNA Topology Tumors |
| title | Low‐Energy Electron‐Induced Strand Breaks in Telomere‐Derived DNA Sequences—Influence of DNA Sequence and Topology |
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