DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans
DNA-protein crosslinks (DPCs) are a specific type of DNA lesion consisting of a protein covalently and irreversibly bound to DNA, which arise after exposure to physical and chemical crosslinking agents. DPCs can be bulky and thereby pose a barrier to DNA replication and transcription. The persistenc...
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| Veröffentlicht in: | DNA repair 2018-11, Vol.71, p.198-204 |
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| creator | Fielden, John Ruggiano, Annamaria Popović, Marta Ramadan, Kristijan |
| description | DNA-protein crosslinks (DPCs) are a specific type of DNA lesion consisting of a protein covalently and irreversibly bound to DNA, which arise after exposure to physical and chemical crosslinking agents. DPCs can be bulky and thereby pose a barrier to DNA replication and transcription. The persistence of DPCs during S phase causes DNA replication stress and genome instability. The toxicity of DPCs is exploited in cancer therapy: many common chemotherapeutics kill cancer cells by inducing DPC formation.
Recent work from several laboratories discovered a specialized repair pathway for DPCs, namely DPC proteolysis (DPCP) repair. DPCP repair is carried out by replication-coupled DNA-dependent metalloproteases: Wss1 in yeast and SPRTN in metazoans. Mutations in SPRTN cause premature ageing and liver cancer in humans and mice; thus, defective DPC repair has great clinical ramifications. In the present review, we will revise the current knowledge on the mechanisms of DPCP repair and on the regulation of DPC protease activity, while highlighting the most significant unresolved questions in the field. Finally, we will discuss the impact of faulty DPC repair on disease and cancer therapy. |
| doi_str_mv | 10.1016/j.dnarep.2018.08.025 |
| format | Article |
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Recent work from several laboratories discovered a specialized repair pathway for DPCs, namely DPC proteolysis (DPCP) repair. DPCP repair is carried out by replication-coupled DNA-dependent metalloproteases: Wss1 in yeast and SPRTN in metazoans. Mutations in SPRTN cause premature ageing and liver cancer in humans and mice; thus, defective DPC repair has great clinical ramifications. In the present review, we will revise the current knowledge on the mechanisms of DPCP repair and on the regulation of DPC protease activity, while highlighting the most significant unresolved questions in the field. Finally, we will discuss the impact of faulty DPC repair on disease and cancer therapy.</description><identifier>ISSN: 1568-7864</identifier><identifier>EISSN: 1568-7856</identifier><identifier>DOI: 10.1016/j.dnarep.2018.08.025</identifier><identifier>PMID: 30170832</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Ageing ; Animals ; Cancer ; Cross-Linking Reagents - pharmacology ; Cross-Linking Reagents - toxicity ; DNA - drug effects ; DNA - radiation effects ; DNA Adducts - metabolism ; DNA Repair ; DNA-Binding Proteins - drug effects ; DNA-Binding Proteins - metabolism ; DNA-Binding Proteins - radiation effects ; DNA-protein crosslinks ; Eukaryota - drug effects ; Eukaryota - genetics ; Eukaryota - metabolism ; Eukaryota - radiation effects ; Genome stability ; Humans ; Post-translational modification ; Proteolysis ; Saccharomyces cerevisiae - drug effects ; Saccharomyces cerevisiae - enzymology ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - radiation effects ; Saccharomyces cerevisiae Proteins - metabolism ; SPRTN protease</subject><ispartof>DNA repair, 2018-11, Vol.71, p.198-204</ispartof><rights>2018</rights><rights>Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.</rights><rights>Crown Copyright © 2018 Published by Elsevier B.V. All rights reserved. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-7834c862190d36dfce8cea0caafaf1a16aca100a16c66006fe51740798ecdf733</citedby><cites>FETCH-LOGICAL-c463t-7834c862190d36dfce8cea0caafaf1a16aca100a16c66006fe51740798ecdf733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1568786418301903$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30170832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fielden, John</creatorcontrib><creatorcontrib>Ruggiano, Annamaria</creatorcontrib><creatorcontrib>Popović, Marta</creatorcontrib><creatorcontrib>Ramadan, Kristijan</creatorcontrib><title>DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans</title><title>DNA repair</title><addtitle>DNA Repair (Amst)</addtitle><description>DNA-protein crosslinks (DPCs) are a specific type of DNA lesion consisting of a protein covalently and irreversibly bound to DNA, which arise after exposure to physical and chemical crosslinking agents. DPCs can be bulky and thereby pose a barrier to DNA replication and transcription. The persistence of DPCs during S phase causes DNA replication stress and genome instability. The toxicity of DPCs is exploited in cancer therapy: many common chemotherapeutics kill cancer cells by inducing DPC formation.
Recent work from several laboratories discovered a specialized repair pathway for DPCs, namely DPC proteolysis (DPCP) repair. DPCP repair is carried out by replication-coupled DNA-dependent metalloproteases: Wss1 in yeast and SPRTN in metazoans. Mutations in SPRTN cause premature ageing and liver cancer in humans and mice; thus, defective DPC repair has great clinical ramifications. In the present review, we will revise the current knowledge on the mechanisms of DPCP repair and on the regulation of DPC protease activity, while highlighting the most significant unresolved questions in the field. Finally, we will discuss the impact of faulty DPC repair on disease and cancer therapy.</description><subject>Ageing</subject><subject>Animals</subject><subject>Cancer</subject><subject>Cross-Linking Reagents - pharmacology</subject><subject>Cross-Linking Reagents - toxicity</subject><subject>DNA - drug effects</subject><subject>DNA - radiation effects</subject><subject>DNA Adducts - metabolism</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - drug effects</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>DNA-Binding Proteins - radiation effects</subject><subject>DNA-protein crosslinks</subject><subject>Eukaryota - drug effects</subject><subject>Eukaryota - genetics</subject><subject>Eukaryota - metabolism</subject><subject>Eukaryota - radiation effects</subject><subject>Genome stability</subject><subject>Humans</subject><subject>Post-translational modification</subject><subject>Proteolysis</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Saccharomyces cerevisiae - enzymology</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - radiation effects</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>SPRTN protease</subject><issn>1568-7864</issn><issn>1568-7856</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kN1KAzEQhYMotlbfQCQv0HWyP9mtF0KpVoWiN3opYczOtqn7U5JtoW9v6mrVG2EgwyTnnMnH2LmAQICQl8sgr9HSKghBZAH4CpMD1heJzIZplsjDfS_jHjtxbgkgklTKY9aLQKSQRWGfvd48jvnKNi2ZmmvbOFea-r2bNOXWGcd9Bhp7xae2qfiW0LW8bfwLqrBdW-I499o5xzrnGmtNlnurxbrC2p2yowJLR2df54C9TG-fJ_fD2dPdw2Q8G-pYRq1fMYp1JkMxgjySeaEp04SgEQssBAqJGgWAb7SUALKgRKQxpKOMdF6kUTRg153vav1WUa6pbi2WamVNhXarGjTq701tFmrebNQuM05CbxB3Bp8ILBV7rQC1w62WqsOtdrgV-AoTL7v4nbsXffP9WYz87zeGrHLakIeUG0u6VXlj_k_4ACrUlhw</recordid><startdate>201811</startdate><enddate>201811</enddate><creator>Fielden, John</creator><creator>Ruggiano, Annamaria</creator><creator>Popović, Marta</creator><creator>Ramadan, Kristijan</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>201811</creationdate><title>DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans</title><author>Fielden, John ; Ruggiano, Annamaria ; Popović, Marta ; Ramadan, Kristijan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-7834c862190d36dfce8cea0caafaf1a16aca100a16c66006fe51740798ecdf733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Ageing</topic><topic>Animals</topic><topic>Cancer</topic><topic>Cross-Linking Reagents - pharmacology</topic><topic>Cross-Linking Reagents - toxicity</topic><topic>DNA - drug effects</topic><topic>DNA - radiation effects</topic><topic>DNA Adducts - metabolism</topic><topic>DNA Repair</topic><topic>DNA-Binding Proteins - drug effects</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>DNA-Binding Proteins - radiation effects</topic><topic>DNA-protein crosslinks</topic><topic>Eukaryota - drug effects</topic><topic>Eukaryota - genetics</topic><topic>Eukaryota - metabolism</topic><topic>Eukaryota - radiation effects</topic><topic>Genome stability</topic><topic>Humans</topic><topic>Post-translational modification</topic><topic>Proteolysis</topic><topic>Saccharomyces cerevisiae - drug effects</topic><topic>Saccharomyces cerevisiae - enzymology</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - radiation effects</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>SPRTN protease</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fielden, John</creatorcontrib><creatorcontrib>Ruggiano, Annamaria</creatorcontrib><creatorcontrib>Popović, Marta</creatorcontrib><creatorcontrib>Ramadan, Kristijan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>DNA repair</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fielden, John</au><au>Ruggiano, Annamaria</au><au>Popović, Marta</au><au>Ramadan, Kristijan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans</atitle><jtitle>DNA repair</jtitle><addtitle>DNA Repair (Amst)</addtitle><date>2018-11</date><risdate>2018</risdate><volume>71</volume><spage>198</spage><epage>204</epage><pages>198-204</pages><issn>1568-7864</issn><eissn>1568-7856</eissn><abstract>DNA-protein crosslinks (DPCs) are a specific type of DNA lesion consisting of a protein covalently and irreversibly bound to DNA, which arise after exposure to physical and chemical crosslinking agents. DPCs can be bulky and thereby pose a barrier to DNA replication and transcription. The persistence of DPCs during S phase causes DNA replication stress and genome instability. The toxicity of DPCs is exploited in cancer therapy: many common chemotherapeutics kill cancer cells by inducing DPC formation.
Recent work from several laboratories discovered a specialized repair pathway for DPCs, namely DPC proteolysis (DPCP) repair. DPCP repair is carried out by replication-coupled DNA-dependent metalloproteases: Wss1 in yeast and SPRTN in metazoans. Mutations in SPRTN cause premature ageing and liver cancer in humans and mice; thus, defective DPC repair has great clinical ramifications. In the present review, we will revise the current knowledge on the mechanisms of DPCP repair and on the regulation of DPC protease activity, while highlighting the most significant unresolved questions in the field. Finally, we will discuss the impact of faulty DPC repair on disease and cancer therapy.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30170832</pmid><doi>10.1016/j.dnarep.2018.08.025</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Ageing Animals Cancer Cross-Linking Reagents - pharmacology Cross-Linking Reagents - toxicity DNA - drug effects DNA - radiation effects DNA Adducts - metabolism DNA Repair DNA-Binding Proteins - drug effects DNA-Binding Proteins - metabolism DNA-Binding Proteins - radiation effects DNA-protein crosslinks Eukaryota - drug effects Eukaryota - genetics Eukaryota - metabolism Eukaryota - radiation effects Genome stability Humans Post-translational modification Proteolysis Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - radiation effects Saccharomyces cerevisiae Proteins - metabolism SPRTN protease |
| title | DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans |
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