PrimPol Bypasses UV Photoproducts during Eukaryotic Chromosomal DNA Replication
DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (Pri...
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| Veröffentlicht in: | Molecular cell 2013-11, Vol.52 (4), p.566-573 |
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| creator | Bianchi, Julie Rudd, Sean G. Jozwiakowski, Stanislaw K. Bailey, Laura J. Soura, Violetta Taylor, Elaine Stevanovic, Irena Green, Andrew J. Stracker, Travis H. Lindsay, Howard D. Doherty, Aidan J. |
| description | DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) light-damaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol η-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells.
[Display omitted]
•PrimPol is a DNA primase-polymerase catalyzing bypass of UV and oxidative lesions•PrimPol operates in a UV lesion tolerance pathway that is non-epistatic with Pol η•PrimPol null cells are defective in fork progression, particularly after UV treatment•Loss of PrimPol leads to increased mitotic chromosomal breaks |
| doi_str_mv | 10.1016/j.molcel.2013.10.035 |
| format | Article |
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[Display omitted]
•PrimPol is a DNA primase-polymerase catalyzing bypass of UV and oxidative lesions•PrimPol operates in a UV lesion tolerance pathway that is non-epistatic with Pol η•PrimPol null cells are defective in fork progression, particularly after UV treatment•Loss of PrimPol leads to increased mitotic chromosomal breaks</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2013.10.035</identifier><identifier>PMID: 24267451</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Cell Proliferation ; Cell Survival ; Chickens ; Chromosomes, Human - genetics ; cytotoxicity ; DNA ; DNA Adducts - chemistry ; DNA Adducts - genetics ; DNA Adducts - metabolism ; DNA Damage ; DNA Primase - chemistry ; DNA Primase - physiology ; DNA Replication ; DNA, Single-Stranded - chemistry ; DNA-Directed DNA Polymerase - chemistry ; DNA-Directed DNA Polymerase - physiology ; enzymes ; epistasis ; eukaryotic cells ; G2 Phase Cell Cycle Checkpoints ; Gene Knockdown Techniques ; genome ; HEK293 Cells ; Humans ; interphase ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Multifunctional Enzymes - chemistry ; Multifunctional Enzymes - physiology ; patients ; photosensitivity disorders ; Short ; Ultraviolet Rays ; Xenopus</subject><ispartof>Molecular cell, 2013-11, Vol.52 (4), p.566-573</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><rights>Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved. 2013 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c595t-a7ef498bd10c82362e829c2a184cf3f195a5a296b153d45c1e7bb9e50b5f96a53</citedby><cites>FETCH-LOGICAL-c595t-a7ef498bd10c82362e829c2a184cf3f195a5a296b153d45c1e7bb9e50b5f96a53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276513008010$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24267451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bianchi, Julie</creatorcontrib><creatorcontrib>Rudd, Sean G.</creatorcontrib><creatorcontrib>Jozwiakowski, Stanislaw K.</creatorcontrib><creatorcontrib>Bailey, Laura J.</creatorcontrib><creatorcontrib>Soura, Violetta</creatorcontrib><creatorcontrib>Taylor, Elaine</creatorcontrib><creatorcontrib>Stevanovic, Irena</creatorcontrib><creatorcontrib>Green, Andrew J.</creatorcontrib><creatorcontrib>Stracker, Travis H.</creatorcontrib><creatorcontrib>Lindsay, Howard D.</creatorcontrib><creatorcontrib>Doherty, Aidan J.</creatorcontrib><title>PrimPol Bypasses UV Photoproducts during Eukaryotic Chromosomal DNA Replication</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) light-damaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol η-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells.
[Display omitted]
•PrimPol is a DNA primase-polymerase catalyzing bypass of UV and oxidative lesions•PrimPol operates in a UV lesion tolerance pathway that is non-epistatic with Pol η•PrimPol null cells are defective in fork progression, particularly after UV treatment•Loss of PrimPol leads to increased mitotic chromosomal breaks</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Chickens</subject><subject>Chromosomes, Human - genetics</subject><subject>cytotoxicity</subject><subject>DNA</subject><subject>DNA Adducts - chemistry</subject><subject>DNA Adducts - genetics</subject><subject>DNA Adducts - metabolism</subject><subject>DNA Damage</subject><subject>DNA Primase - chemistry</subject><subject>DNA Primase - physiology</subject><subject>DNA Replication</subject><subject>DNA, Single-Stranded - chemistry</subject><subject>DNA-Directed DNA Polymerase - chemistry</subject><subject>DNA-Directed DNA Polymerase - physiology</subject><subject>enzymes</subject><subject>epistasis</subject><subject>eukaryotic cells</subject><subject>G2 Phase Cell Cycle Checkpoints</subject><subject>Gene Knockdown Techniques</subject><subject>genome</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>interphase</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular Sequence Data</subject><subject>Multifunctional Enzymes - chemistry</subject><subject>Multifunctional Enzymes - physiology</subject><subject>patients</subject><subject>photosensitivity disorders</subject><subject>Short</subject><subject>Ultraviolet Rays</subject><subject>Xenopus</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUcFO3DAQtVAroNA_QCjHXnZrOx4nviDBFlokVFao9Go5zoT1NolTO0Hi7_Fqt9Beii9jzbx5M_MeISeMzhll8vN63vnWYjvnlOUpNac57JFDRlUxE0yKd7s_LyQckA8xrillAkq1Tw644LIQwA7J7TK4bunb7OJpMDFizO5_ZsuVH_0QfD3ZMWb1FFz_kF1Ov0x48qOz2WIVfOej70ybffl-nt3h0DprRuf7Y_K-MW3Ej7t4RO6vLn8svs1ubr9eL85vZhYUjDNTYCNUWdWM2pLnkmPJleWGlcI2ecMUGDBcyYpBXguwDIuqUgi0gkZJA_kROdvyDlPVYW2xH4Np9ZCuSVtqb5z-t9K7lX7wj1pwXlJRJIJPO4Lgf08YR925mORsTY9-iprT9BRwgDehDCjkvOD526xMSFYWSqoyQcUWaoOPMWDzsjyjeuOwXuutw3rj8CabHE5tp38f_tL0x9JXZTDJ_-gw6Ggd9hZrF9COuvbu_xOeAS2Iuac</recordid><startdate>20131121</startdate><enddate>20131121</enddate><creator>Bianchi, Julie</creator><creator>Rudd, Sean G.</creator><creator>Jozwiakowski, Stanislaw K.</creator><creator>Bailey, Laura J.</creator><creator>Soura, Violetta</creator><creator>Taylor, Elaine</creator><creator>Stevanovic, Irena</creator><creator>Green, Andrew J.</creator><creator>Stracker, Travis H.</creator><creator>Lindsay, Howard D.</creator><creator>Doherty, Aidan J.</creator><general>Elsevier Inc</general><general>Cell Press</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>7X8</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20131121</creationdate><title>PrimPol Bypasses UV Photoproducts during Eukaryotic Chromosomal DNA Replication</title><author>Bianchi, Julie ; Rudd, Sean G. ; Jozwiakowski, Stanislaw K. ; Bailey, Laura J. ; Soura, Violetta ; Taylor, Elaine ; Stevanovic, Irena ; Green, Andrew J. ; Stracker, Travis H. ; Lindsay, Howard D. ; Doherty, Aidan J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c595t-a7ef498bd10c82362e829c2a184cf3f195a5a296b153d45c1e7bb9e50b5f96a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Chickens</topic><topic>Chromosomes, Human - genetics</topic><topic>cytotoxicity</topic><topic>DNA</topic><topic>DNA Adducts - chemistry</topic><topic>DNA Adducts - genetics</topic><topic>DNA Adducts - metabolism</topic><topic>DNA Damage</topic><topic>DNA Primase - chemistry</topic><topic>DNA Primase - physiology</topic><topic>DNA Replication</topic><topic>DNA, Single-Stranded - chemistry</topic><topic>DNA-Directed DNA Polymerase - chemistry</topic><topic>DNA-Directed DNA Polymerase - physiology</topic><topic>enzymes</topic><topic>epistasis</topic><topic>eukaryotic cells</topic><topic>G2 Phase Cell Cycle Checkpoints</topic><topic>Gene Knockdown Techniques</topic><topic>genome</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>interphase</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular Sequence Data</topic><topic>Multifunctional Enzymes - chemistry</topic><topic>Multifunctional Enzymes - physiology</topic><topic>patients</topic><topic>photosensitivity disorders</topic><topic>Short</topic><topic>Ultraviolet Rays</topic><topic>Xenopus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bianchi, Julie</creatorcontrib><creatorcontrib>Rudd, Sean G.</creatorcontrib><creatorcontrib>Jozwiakowski, Stanislaw K.</creatorcontrib><creatorcontrib>Bailey, Laura J.</creatorcontrib><creatorcontrib>Soura, Violetta</creatorcontrib><creatorcontrib>Taylor, Elaine</creatorcontrib><creatorcontrib>Stevanovic, Irena</creatorcontrib><creatorcontrib>Green, Andrew J.</creatorcontrib><creatorcontrib>Stracker, Travis H.</creatorcontrib><creatorcontrib>Lindsay, Howard D.</creatorcontrib><creatorcontrib>Doherty, Aidan J.</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>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bianchi, Julie</au><au>Rudd, Sean G.</au><au>Jozwiakowski, Stanislaw K.</au><au>Bailey, Laura J.</au><au>Soura, Violetta</au><au>Taylor, Elaine</au><au>Stevanovic, Irena</au><au>Green, Andrew J.</au><au>Stracker, Travis H.</au><au>Lindsay, Howard D.</au><au>Doherty, Aidan J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PrimPol Bypasses UV Photoproducts during Eukaryotic Chromosomal DNA Replication</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2013-11-21</date><risdate>2013</risdate><volume>52</volume><issue>4</issue><spage>566</spage><epage>573</epage><pages>566-573</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) light-damaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol η-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells.
[Display omitted]
•PrimPol is a DNA primase-polymerase catalyzing bypass of UV and oxidative lesions•PrimPol operates in a UV lesion tolerance pathway that is non-epistatic with Pol η•PrimPol null cells are defective in fork progression, particularly after UV treatment•Loss of PrimPol leads to increased mitotic chromosomal breaks</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24267451</pmid><doi>10.1016/j.molcel.2013.10.035</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Animals Cell Proliferation Cell Survival Chickens Chromosomes, Human - genetics cytotoxicity DNA DNA Adducts - chemistry DNA Adducts - genetics DNA Adducts - metabolism DNA Damage DNA Primase - chemistry DNA Primase - physiology DNA Replication DNA, Single-Stranded - chemistry DNA-Directed DNA Polymerase - chemistry DNA-Directed DNA Polymerase - physiology enzymes epistasis eukaryotic cells G2 Phase Cell Cycle Checkpoints Gene Knockdown Techniques genome HEK293 Cells Humans interphase Mice Mice, Knockout Molecular Sequence Data Multifunctional Enzymes - chemistry Multifunctional Enzymes - physiology patients photosensitivity disorders Short Ultraviolet Rays Xenopus |
| title | PrimPol Bypasses UV Photoproducts during Eukaryotic Chromosomal DNA Replication |
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