Roles of eukaryotic topoisomerases in transcription, replication and genomic stability
Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, thereby mediating chromatin dynamics and stability, transcription, replication and DNA damage repair. Topoisomerases are targets of various anticancer drugs, and their deregulation can cause, in addition to cancer, neurodegenera...
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| Veröffentlicht in: | Nature reviews. Molecular cell biology 2016-11, Vol.17 (11), p.703-721 |
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| creator | Pommier, Yves Sun, Yilun Huang, Shar-yin N. Nitiss, John L. |
| description | Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, thereby mediating chromatin dynamics and stability, transcription, replication and DNA damage repair. Topoisomerases are targets of various anticancer drugs, and their deregulation can cause, in addition to cancer, neurodegenerative diseases and immune disorders.
Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3α and TOP3β), which act on a broad range of DNA and RNA substrates at the nuclear and mitochondrial genomes. Their catalytic intermediates, the topoisomerase cleavage complexes (TOPcc), are therapeutic targets of various anticancer drugs. TOPcc can also form on damaged DNA during replication and transcription, and engage specific repair pathways, such as those mediated by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 and by endonucleases (MRE11, XPF–ERCC1 and MUS81). Here, we review the roles of topoisomerases in mediating chromatin dynamics, transcription, replication, DNA damage repair and genomic stability, and discuss how deregulation of topoisomerases can cause neurodegenerative diseases, immune disorders and cancer. |
| doi_str_mv | 10.1038/nrm.2016.111 |
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Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3α and TOP3β), which act on a broad range of DNA and RNA substrates at the nuclear and mitochondrial genomes. Their catalytic intermediates, the topoisomerase cleavage complexes (TOPcc), are therapeutic targets of various anticancer drugs. TOPcc can also form on damaged DNA during replication and transcription, and engage specific repair pathways, such as those mediated by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 and by endonucleases (MRE11, XPF–ERCC1 and MUS81). Here, we review the roles of topoisomerases in mediating chromatin dynamics, transcription, replication, DNA damage repair and genomic stability, and discuss how deregulation of topoisomerases can cause neurodegenerative diseases, immune disorders and cancer.</description><identifier>ISSN: 1471-0072</identifier><identifier>EISSN: 1471-0080</identifier><identifier>DOI: 10.1038/nrm.2016.111</identifier><identifier>PMID: 27649880</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/211 ; 631/337/151 ; 631/337/572 ; Animals ; Biochemistry ; Cancer ; Cancer Research ; Cell Biology ; Cell division ; Chemotherapy ; Deoxyribonucleic acid ; Deregulation ; Developmental Biology ; Disease susceptibility ; DNA ; DNA Damage ; DNA Repair ; DNA Replication ; DNA Topoisomerases - physiology ; Enzymes ; Genetic aspects ; Genetic transcription ; Genomes ; Genomic Instability ; Health aspects ; Humans ; Life Sciences ; Medical research ; Mitochondria - enzymology ; Mitochondria - genetics ; Phosphate esters ; Properties ; review-article ; Stem Cells ; Topoisomerases ; Transcription, Genetic</subject><ispartof>Nature reviews. Molecular cell biology, 2016-11, Vol.17 (11), p.703-721</ispartof><rights>Springer Nature Limited 2016</rights><rights>COPYRIGHT 2016 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Nov 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c650t-c585a3b3a2fc4ef7afbf993293c139e8d9320d40921ad8a447885de93f3525283</citedby><cites>FETCH-LOGICAL-c650t-c585a3b3a2fc4ef7afbf993293c139e8d9320d40921ad8a447885de93f3525283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nrm.2016.111$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nrm.2016.111$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27649880$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pommier, Yves</creatorcontrib><creatorcontrib>Sun, Yilun</creatorcontrib><creatorcontrib>Huang, Shar-yin N.</creatorcontrib><creatorcontrib>Nitiss, John L.</creatorcontrib><title>Roles of eukaryotic topoisomerases in transcription, replication and genomic stability</title><title>Nature reviews. Molecular cell biology</title><addtitle>Nat Rev Mol Cell Biol</addtitle><addtitle>Nat Rev Mol Cell Biol</addtitle><description>Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, thereby mediating chromatin dynamics and stability, transcription, replication and DNA damage repair. Topoisomerases are targets of various anticancer drugs, and their deregulation can cause, in addition to cancer, neurodegenerative diseases and immune disorders.
Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3α and TOP3β), which act on a broad range of DNA and RNA substrates at the nuclear and mitochondrial genomes. Their catalytic intermediates, the topoisomerase cleavage complexes (TOPcc), are therapeutic targets of various anticancer drugs. TOPcc can also form on damaged DNA during replication and transcription, and engage specific repair pathways, such as those mediated by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 and by endonucleases (MRE11, XPF–ERCC1 and MUS81). Here, we review the roles of topoisomerases in mediating chromatin dynamics, transcription, replication, DNA damage repair and genomic stability, and discuss how deregulation of topoisomerases can cause neurodegenerative diseases, immune disorders and cancer.</description><subject>631/208/211</subject><subject>631/337/151</subject><subject>631/337/572</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell division</subject><subject>Chemotherapy</subject><subject>Deoxyribonucleic acid</subject><subject>Deregulation</subject><subject>Developmental Biology</subject><subject>Disease susceptibility</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA Repair</subject><subject>DNA Replication</subject><subject>DNA Topoisomerases - physiology</subject><subject>Enzymes</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Genomes</subject><subject>Genomic Instability</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Medical research</subject><subject>Mitochondria - enzymology</subject><subject>Mitochondria - genetics</subject><subject>Phosphate esters</subject><subject>Properties</subject><subject>review-article</subject><subject>Stem Cells</subject><subject>Topoisomerases</subject><subject>Transcription, Genetic</subject><issn>1471-0072</issn><issn>1471-0080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkstv1DAQxi0EomXhxhlF4gJSs_gRb-wLUlXxqFQJqTyultcZB5fETm0H0f8eR1uWLuoB-eCx5zefZj4NQs8JXhPMxBsfxzXFZLMmhDxAx6RpSY2xwA_3cUuP0JOUrnChSMsfoyPabhopBD5G3y7DAKkKtoL5h443ITtT5TAFl8IIUaeSdL7KUftkopuyC_6kijANzujlUWnfVT34MJbClPXWDS7fPEWPrB4SPLu9V-jr-3dfzj7WF58-nJ-dXtRmw3GuDRdcsy3T1JoGbKvt1krJqGSGMAmiKzHuGiwp0Z3QTdMKwTuQzDJOORVshd7udKd5O0JnwJdOBzVFN5ZhVNBOHWa8-6768FNJ2gjWLAKvbgViuJ4hZTW6ZGAYtIcwJ0UEaxkr1rL_QTnjuMgW9OU_6FWYoy9OLBQVQlKK_1K9HkA5b0Np0Syi6rTZtIQS3i5a63uocjoolgcP1pX_g4LXBwWFyfAr93pOSZ1_vjxkT3asiSGlCHZvHcFqWS9V1kst66UWD1boxV279_CffSpAvQNSSfke4p3B7xP8Dca32Hk</recordid><startdate>20161101</startdate><enddate>20161101</enddate><creator>Pommier, Yves</creator><creator>Sun, Yilun</creator><creator>Huang, Shar-yin N.</creator><creator>Nitiss, John L.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161101</creationdate><title>Roles of eukaryotic topoisomerases in transcription, replication and genomic stability</title><author>Pommier, Yves ; 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Molecular cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pommier, Yves</au><au>Sun, Yilun</au><au>Huang, Shar-yin N.</au><au>Nitiss, John L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Roles of eukaryotic topoisomerases in transcription, replication and genomic stability</atitle><jtitle>Nature reviews. Molecular cell biology</jtitle><stitle>Nat Rev Mol Cell Biol</stitle><addtitle>Nat Rev Mol Cell Biol</addtitle><date>2016-11-01</date><risdate>2016</risdate><volume>17</volume><issue>11</issue><spage>703</spage><epage>721</epage><pages>703-721</pages><issn>1471-0072</issn><eissn>1471-0080</eissn><abstract>Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, thereby mediating chromatin dynamics and stability, transcription, replication and DNA damage repair. Topoisomerases are targets of various anticancer drugs, and their deregulation can cause, in addition to cancer, neurodegenerative diseases and immune disorders.
Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3α and TOP3β), which act on a broad range of DNA and RNA substrates at the nuclear and mitochondrial genomes. Their catalytic intermediates, the topoisomerase cleavage complexes (TOPcc), are therapeutic targets of various anticancer drugs. TOPcc can also form on damaged DNA during replication and transcription, and engage specific repair pathways, such as those mediated by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 and by endonucleases (MRE11, XPF–ERCC1 and MUS81). Here, we review the roles of topoisomerases in mediating chromatin dynamics, transcription, replication, DNA damage repair and genomic stability, and discuss how deregulation of topoisomerases can cause neurodegenerative diseases, immune disorders and cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27649880</pmid><doi>10.1038/nrm.2016.111</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/208/211 631/337/151 631/337/572 Animals Biochemistry Cancer Cancer Research Cell Biology Cell division Chemotherapy Deoxyribonucleic acid Deregulation Developmental Biology Disease susceptibility DNA DNA Damage DNA Repair DNA Replication DNA Topoisomerases - physiology Enzymes Genetic aspects Genetic transcription Genomes Genomic Instability Health aspects Humans Life Sciences Medical research Mitochondria - enzymology Mitochondria - genetics Phosphate esters Properties review-article Stem Cells Topoisomerases Transcription, Genetic |
| title | Roles of eukaryotic topoisomerases in transcription, replication and genomic stability |
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