Never-in-mitosis related Kinase 1 functions in DNA damage response and checkpoint control
Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of dam...
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| Veröffentlicht in: | Cell cycle (Georgetown, Tex.) Tex.), 2008-10, Vol.7 (20), p.3194-3201 |
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| creator | Chen, Yumay Chen, Phang-Lang Chen, Chi-Fen Jiang, Xianzhi Riley, Daniel J. |
| description | Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1 -/- mice fail to arrest properly at G1/S and M-phase checkpoints in response to DNA damage. G1-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1-/- murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair. |
| doi_str_mv | 10.4161/cc.7.20.6815 |
| format | Article |
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Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1 -/- mice fail to arrest properly at G1/S and M-phase checkpoints in response to DNA damage. G1-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1-/- murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair.</description><identifier>ISSN: 1538-4101</identifier><identifier>EISSN: 1551-4005</identifier><identifier>DOI: 10.4161/cc.7.20.6815</identifier><identifier>PMID: 18843199</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Binding ; Biology ; Bioscience ; Calcium ; Cancer ; Cell ; Cell Cycle - physiology ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Line ; Checkpoint Kinase 1 ; Checkpoint Kinase 2 ; Cycle ; DNA - drug effects ; DNA - radiation effects ; DNA Damage ; DNA Repair ; Enzyme Activation ; Humans ; Landes ; Mice ; Mice, Knockout ; NIMA-Related Kinase 1 ; Organogenesis ; Protein Kinases - genetics ; Protein Kinases - metabolism ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; Radiation, Ionizing ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; RNA Interference ; Ultraviolet Rays</subject><ispartof>Cell cycle (Georgetown, Tex.), 2008-10, Vol.7 (20), p.3194-3201</ispartof><rights>Copyright © 2008 Landes Bioscience 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-5389eee398bb64ef4613bbddc4bf61c966140fe18937e733cb9648316e2d74133</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18843199$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yumay</creatorcontrib><creatorcontrib>Chen, Phang-Lang</creatorcontrib><creatorcontrib>Chen, Chi-Fen</creatorcontrib><creatorcontrib>Jiang, Xianzhi</creatorcontrib><creatorcontrib>Riley, Daniel J.</creatorcontrib><title>Never-in-mitosis related Kinase 1 functions in DNA damage response and checkpoint control</title><title>Cell cycle (Georgetown, Tex.)</title><addtitle>Cell Cycle</addtitle><description>Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1 -/- mice fail to arrest properly at G1/S and M-phase checkpoints in response to DNA damage. G1-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1-/- murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair.</description><subject>Animals</subject><subject>Binding</subject><subject>Biology</subject><subject>Bioscience</subject><subject>Calcium</subject><subject>Cancer</subject><subject>Cell</subject><subject>Cell Cycle - physiology</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line</subject><subject>Checkpoint Kinase 1</subject><subject>Checkpoint Kinase 2</subject><subject>Cycle</subject><subject>DNA - drug effects</subject><subject>DNA - radiation effects</subject><subject>DNA Damage</subject><subject>DNA Repair</subject><subject>Enzyme Activation</subject><subject>Humans</subject><subject>Landes</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>NIMA-Related Kinase 1</subject><subject>Organogenesis</subject><subject>Protein Kinases - genetics</subject><subject>Protein Kinases - metabolism</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Radiation, Ionizing</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>RNA Interference</subject><subject>Ultraviolet Rays</subject><issn>1538-4101</issn><issn>1551-4005</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><recordid>eNptkc1v1DAQxSMEoqVw44x84kS2ntix4wtSVb4qqnKBAyfLmUxaQ2Ivdrao_z1edmmp1JNHnt-89zRTVS-BryQoOEZc6VXDV6qD9lF1CG0LteS8fbytRVdL4HBQPcv5B-dNpw08rQ6g66QAYw6r7xd0Tan2oZ79ErPPLNHkFhrYZx9cJgZs3ARcfAyZ-cDeXZywwc3ukgqY1-WXmAsDwyvCn-vow8IwhiXF6Xn1ZHRTphf796j69uH919NP9fmXj2enJ-c1Ss2XukQ0RCRM1_dK0igViL4fBpT9qACNUiD5SNAZoUkLgb1RshOgqBm0BCGOqrc73fWmn2lAKu5usuvkZ5dubHTe3u8Ef2Uv47VtWqPBQBF4vRdI8deG8mJnn5GmyQWKm2yVKavt_oJvdiCmmHOi8dYEuN3ewiJabRtut7co-Kv_g93B--UX4HgHFKeBcu9jRk8B6RYtei4tHif6J6l3Ez6MMc3ud0zTYBd3M8U0JhfQZyseDPMH0BqqTg</recordid><startdate>20081015</startdate><enddate>20081015</enddate><creator>Chen, Yumay</creator><creator>Chen, Phang-Lang</creator><creator>Chen, Chi-Fen</creator><creator>Jiang, Xianzhi</creator><creator>Riley, Daniel J.</creator><general>Taylor & Francis</general><scope>0YH</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>5PM</scope></search><sort><creationdate>20081015</creationdate><title>Never-in-mitosis related Kinase 1 functions in DNA damage response and checkpoint control</title><author>Chen, Yumay ; Chen, Phang-Lang ; Chen, Chi-Fen ; Jiang, Xianzhi ; Riley, Daniel J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-5389eee398bb64ef4613bbddc4bf61c966140fe18937e733cb9648316e2d74133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Binding</topic><topic>Biology</topic><topic>Bioscience</topic><topic>Calcium</topic><topic>Cancer</topic><topic>Cell</topic><topic>Cell Cycle - physiology</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Line</topic><topic>Checkpoint Kinase 1</topic><topic>Checkpoint Kinase 2</topic><topic>Cycle</topic><topic>DNA - drug effects</topic><topic>DNA - radiation effects</topic><topic>DNA Damage</topic><topic>DNA Repair</topic><topic>Enzyme Activation</topic><topic>Humans</topic><topic>Landes</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>NIMA-Related Kinase 1</topic><topic>Organogenesis</topic><topic>Protein Kinases - genetics</topic><topic>Protein Kinases - metabolism</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proteins</topic><topic>Radiation, Ionizing</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>RNA Interference</topic><topic>Ultraviolet Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yumay</creatorcontrib><creatorcontrib>Chen, Phang-Lang</creatorcontrib><creatorcontrib>Chen, Chi-Fen</creatorcontrib><creatorcontrib>Jiang, Xianzhi</creatorcontrib><creatorcontrib>Riley, Daniel J.</creatorcontrib><collection>Taylor & Francis Open Access(OpenAccess)</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>PubMed Central (Full Participant titles)</collection><jtitle>Cell cycle (Georgetown, Tex.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yumay</au><au>Chen, Phang-Lang</au><au>Chen, Chi-Fen</au><au>Jiang, Xianzhi</au><au>Riley, Daniel J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Never-in-mitosis related Kinase 1 functions in DNA damage response and checkpoint control</atitle><jtitle>Cell cycle (Georgetown, Tex.)</jtitle><addtitle>Cell Cycle</addtitle><date>2008-10-15</date><risdate>2008</risdate><volume>7</volume><issue>20</issue><spage>3194</spage><epage>3201</epage><pages>3194-3201</pages><issn>1538-4101</issn><eissn>1551-4005</eissn><abstract>Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1 -/- mice fail to arrest properly at G1/S and M-phase checkpoints in response to DNA damage. G1-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1-/- murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>18843199</pmid><doi>10.4161/cc.7.20.6815</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Binding Biology Bioscience Calcium Cancer Cell Cell Cycle - physiology Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Line Checkpoint Kinase 1 Checkpoint Kinase 2 Cycle DNA - drug effects DNA - radiation effects DNA Damage DNA Repair Enzyme Activation Humans Landes Mice Mice, Knockout NIMA-Related Kinase 1 Organogenesis Protein Kinases - genetics Protein Kinases - metabolism Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proteins Radiation, Ionizing Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism RNA Interference Ultraviolet Rays |
| title | Never-in-mitosis related Kinase 1 functions in DNA damage response and checkpoint control |
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