Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1
The human Tousled-like kinases 1 and 2 (TLK) have been shown to be active during S phase of the cell cycle. TLK activity is rapidly suppressed by DNA damage and by inhibitors of replication. Here we report that the signal transduction pathway, which leads to transient suppression of TLK activity aft...
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| Veröffentlicht in: | Oncogene 2003-09, Vol.22 (38), p.5927-5937 |
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| creator | Krause, Darren R Jonnalagadda, Jyoti C Gatei, Magtouf H Sillje, Herman HW Zhou, Bin-Bing Nigg, Erich A Khanna, Kumkum |
| description | The human Tousled-like kinases 1 and 2 (TLK) have been shown to be active during S phase of the cell cycle. TLK activity is rapidly suppressed by DNA damage and by inhibitors of replication. Here we report that the signal transduction pathway, which leads to transient suppression of TLK activity after the induction of double-strand breaks (DSBs) in the DNA, is dependent on the presence of a functional ataxia-telangiectasia-mutated kinase (ATM). Interestingly, we have discovered that rapid suppression of TLK activity after low doses of ultraviolet (UV) irradiation or aphidicolin-induced replication block is also ATM-dependent. The nature of the signal that triggers ATM-dependent downregulation of TLK activity after UVC and replication block remains unknown, but it is not due exclusively to DSBs in the DNA. We also demonstrate that TLK suppression is dependent on the presence of a functional Nijmegan Breakage Syndrome protein (NBS1). ATM-dependent phosphorylation of NBS1 is required for the suppression of TLK activity, indicating a role for NBS1 as an adaptor or scaffold in the ATM/TLK pathway. ATM does not phosphorylate TLK directly to regulate its activity, but Chk1 does phosphorylate TLK1 GST-fusion proteins
in vitro
. Using Chk1 siRNAs, we show that Chk1 is essential for the suppression of TLK activity after replication block, but that ATR, Chk2 and BRCA1 are dispensable for TLK suppression. Overall, we propose that ATM activation is not linked solely to DSBs and that ATM participates in initiating signaling pathways in response to replication block and UV-induced DNA damage. |
| doi_str_mv | 10.1038/sj.onc.1206691 |
| format | Article |
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in vitro
. Using Chk1 siRNAs, we show that Chk1 is essential for the suppression of TLK activity after replication block, but that ATR, Chk2 and BRCA1 are dispensable for TLK suppression. Overall, we propose that ATM activation is not linked solely to DSBs and that ATM participates in initiating signaling pathways in response to replication block and UV-induced DNA damage.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1206691</identifier><identifier>PMID: 12955071</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adaptor proteins ; Aphidicolin ; Aphidicolin - pharmacology ; Apoptosis ; Ataxia ; Ataxia Telangiectasia Mutated Proteins ; Biological and medical sciences ; BRCA1 protein ; Cell Biology ; Cell cycle ; Cell Cycle Proteins - drug effects ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Cycle Proteins - radiation effects ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cells, Cultured ; Checkpoint Kinase 1 ; CHK1 protein ; CHK2 protein ; Deoxyribonucleic acid ; Diverse techniques ; DNA ; DNA biosynthesis ; DNA damage ; DNA Damage - physiology ; DNA Replication - drug effects ; DNA Replication - radiation effects ; DNA-Binding Proteins ; Dose-Response Relationship, Radiation ; Enzyme Activation - drug effects ; Enzyme Activation - radiation effects ; Fundamental and applied biological sciences. Psychology ; Gamma Rays ; Glutathione Transferase - genetics ; Glutathione Transferase - metabolism ; Human Genetics ; Humans ; Internal Medicine ; Kinases ; Medicine ; Medicine & Public Health ; Molecular and cellular biology ; Nuclear Proteins - drug effects ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Nuclear Proteins - radiation effects ; Oncology ; original-paper ; Phosphorylation ; Protein Kinases - drug effects ; Protein Kinases - genetics ; Protein Kinases - metabolism ; Protein Kinases - radiation effects ; Protein-Serine-Threonine Kinases - drug effects ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Protein-Serine-Threonine Kinases - radiation effects ; Proteins ; Radiation, Ionizing ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Replication ; RNA, Small Interfering - pharmacology ; S phase ; Serine - metabolism ; Signal transduction ; Signal Transduction - drug effects ; Signal Transduction - radiation effects ; siRNA ; Tumor Suppressor Proteins ; Ultraviolet Rays ; Yeast</subject><ispartof>Oncogene, 2003-09, Vol.22 (38), p.5927-5937</ispartof><rights>Springer Nature Limited 2003</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 4, 2003</rights><rights>Nature Publishing Group 2003.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-ee77f1833a16202d196ba59bcd1b15f9afd749317fef1faa36e73ebabafd4bd83</citedby><cites>FETCH-LOGICAL-c508t-ee77f1833a16202d196ba59bcd1b15f9afd749317fef1faa36e73ebabafd4bd83</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/sj.onc.1206691$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1206691$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15101965$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12955071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krause, Darren R</creatorcontrib><creatorcontrib>Jonnalagadda, Jyoti C</creatorcontrib><creatorcontrib>Gatei, Magtouf H</creatorcontrib><creatorcontrib>Sillje, Herman HW</creatorcontrib><creatorcontrib>Zhou, Bin-Bing</creatorcontrib><creatorcontrib>Nigg, Erich A</creatorcontrib><creatorcontrib>Khanna, Kumkum</creatorcontrib><title>Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>The human Tousled-like kinases 1 and 2 (TLK) have been shown to be active during S phase of the cell cycle. TLK activity is rapidly suppressed by DNA damage and by inhibitors of replication. Here we report that the signal transduction pathway, which leads to transient suppression of TLK activity after the induction of double-strand breaks (DSBs) in the DNA, is dependent on the presence of a functional ataxia-telangiectasia-mutated kinase (ATM). Interestingly, we have discovered that rapid suppression of TLK activity after low doses of ultraviolet (UV) irradiation or aphidicolin-induced replication block is also ATM-dependent. The nature of the signal that triggers ATM-dependent downregulation of TLK activity after UVC and replication block remains unknown, but it is not due exclusively to DSBs in the DNA. We also demonstrate that TLK suppression is dependent on the presence of a functional Nijmegan Breakage Syndrome protein (NBS1). ATM-dependent phosphorylation of NBS1 is required for the suppression of TLK activity, indicating a role for NBS1 as an adaptor or scaffold in the ATM/TLK pathway. ATM does not phosphorylate TLK directly to regulate its activity, but Chk1 does phosphorylate TLK1 GST-fusion proteins
in vitro
. Using Chk1 siRNAs, we show that Chk1 is essential for the suppression of TLK activity after replication block, but that ATR, Chk2 and BRCA1 are dispensable for TLK suppression. Overall, we propose that ATM activation is not linked solely to DSBs and that ATM participates in initiating signaling pathways in response to replication block and UV-induced DNA damage.</description><subject>Adaptor proteins</subject><subject>Aphidicolin</subject><subject>Aphidicolin - pharmacology</subject><subject>Apoptosis</subject><subject>Ataxia</subject><subject>Ataxia Telangiectasia Mutated Proteins</subject><subject>Biological and medical sciences</subject><subject>BRCA1 protein</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - drug effects</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Cycle Proteins - radiation effects</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cells, Cultured</subject><subject>Checkpoint Kinase 1</subject><subject>CHK1 protein</subject><subject>CHK2 protein</subject><subject>Deoxyribonucleic acid</subject><subject>Diverse techniques</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA damage</subject><subject>DNA Damage - physiology</subject><subject>DNA Replication - drug effects</subject><subject>DNA Replication - radiation effects</subject><subject>DNA-Binding Proteins</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Activation - radiation effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gamma Rays</subject><subject>Glutathione Transferase - genetics</subject><subject>Glutathione Transferase - metabolism</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular and cellular biology</subject><subject>Nuclear Proteins - drug effects</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nuclear Proteins - radiation effects</subject><subject>Oncology</subject><subject>original-paper</subject><subject>Phosphorylation</subject><subject>Protein Kinases - drug effects</subject><subject>Protein Kinases - genetics</subject><subject>Protein Kinases - metabolism</subject><subject>Protein Kinases - radiation effects</subject><subject>Protein-Serine-Threonine Kinases - drug effects</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Protein-Serine-Threonine Kinases - radiation effects</subject><subject>Proteins</subject><subject>Radiation, Ionizing</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Replication</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>S phase</subject><subject>Serine - metabolism</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - radiation effects</subject><subject>siRNA</subject><subject>Tumor Suppressor Proteins</subject><subject>Ultraviolet Rays</subject><subject>Yeast</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kU2P0zAQhiMEYsvClRvIAsGJdO04juNjKZ_Sshy2nKOJMy5uEztrJ0j773HVSkVIKx8szTzvfL1Z9pLRJaO8voq7pXd6yQpaVYo9yhaslFUuhCofZwuqBM1VwYuL7FmMO0qpVLR4ml2wQglBJVtkw-08jgFjtN4Rb8jGz7HHLu_tHsneOohIQE_2j53uCZgJA_l0syIdDLBF4gMJOPZWw3TQt73X-xS5m20qSVabHx_IzcdbRsB1ZP17z55nTwz0EV-c_svs15fPm_W3_Prn1-_r1XWuBa2nHFFKw2rOgVUFLTqmqhaEanXHWiaMAtPJUnEmDRpmAHiFkmMLbUqUbVfzy-z9se4Y_N2McWoGGzX2PThMCzasrouqkjSBb_8Dd34OLs3WFFXJeFELIRP15kGqkFzwsj70XB6hLfTYWGf8FECn1-FgtXdobIqvWK2Y5IrLs0AHH2NA04zBDhDuG0abg7lN3DXJ3OZkbhK8Po0xtwN2Z_zkZgLenQCIGnoTwGkbz5xgNJ1SJO7qyMWUclsM530ebP3qqHAwzQH_aX3M_wVOGcWl</recordid><startdate>20030904</startdate><enddate>20030904</enddate><creator>Krause, Darren R</creator><creator>Jonnalagadda, Jyoti C</creator><creator>Gatei, Magtouf H</creator><creator>Sillje, Herman HW</creator><creator>Zhou, Bin-Bing</creator><creator>Nigg, Erich A</creator><creator>Khanna, Kumkum</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</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>3V.</scope><scope>7TM</scope><scope>7TO</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>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20030904</creationdate><title>Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1</title><author>Krause, Darren R ; Jonnalagadda, Jyoti C ; Gatei, Magtouf H ; Sillje, Herman HW ; Zhou, Bin-Bing ; Nigg, Erich A ; Khanna, Kumkum</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-ee77f1833a16202d196ba59bcd1b15f9afd749317fef1faa36e73ebabafd4bd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adaptor proteins</topic><topic>Aphidicolin</topic><topic>Aphidicolin - pharmacology</topic><topic>Apoptosis</topic><topic>Ataxia</topic><topic>Ataxia Telangiectasia Mutated Proteins</topic><topic>Biological and medical sciences</topic><topic>BRCA1 protein</topic><topic>Cell Biology</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins - drug effects</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Cycle Proteins - radiation effects</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cells, Cultured</topic><topic>Checkpoint Kinase 1</topic><topic>CHK1 protein</topic><topic>CHK2 protein</topic><topic>Deoxyribonucleic acid</topic><topic>Diverse techniques</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA damage</topic><topic>DNA Damage - physiology</topic><topic>DNA Replication - drug effects</topic><topic>DNA Replication - radiation effects</topic><topic>DNA-Binding Proteins</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Activation - radiation effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gamma Rays</topic><topic>Glutathione Transferase - genetics</topic><topic>Glutathione Transferase - metabolism</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular and cellular biology</topic><topic>Nuclear Proteins - drug effects</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nuclear Proteins - radiation effects</topic><topic>Oncology</topic><topic>original-paper</topic><topic>Phosphorylation</topic><topic>Protein Kinases - drug effects</topic><topic>Protein Kinases - genetics</topic><topic>Protein Kinases - metabolism</topic><topic>Protein Kinases - radiation effects</topic><topic>Protein-Serine-Threonine Kinases - drug effects</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Protein-Serine-Threonine Kinases - radiation effects</topic><topic>Proteins</topic><topic>Radiation, Ionizing</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Replication</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>S phase</topic><topic>Serine - metabolism</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - radiation effects</topic><topic>siRNA</topic><topic>Tumor Suppressor Proteins</topic><topic>Ultraviolet Rays</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krause, Darren R</creatorcontrib><creatorcontrib>Jonnalagadda, Jyoti C</creatorcontrib><creatorcontrib>Gatei, Magtouf H</creatorcontrib><creatorcontrib>Sillje, Herman HW</creatorcontrib><creatorcontrib>Zhou, Bin-Bing</creatorcontrib><creatorcontrib>Nigg, Erich A</creatorcontrib><creatorcontrib>Khanna, Kumkum</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krause, Darren R</au><au>Jonnalagadda, Jyoti C</au><au>Gatei, Magtouf H</au><au>Sillje, Herman HW</au><au>Zhou, Bin-Bing</au><au>Nigg, Erich A</au><au>Khanna, Kumkum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2003-09-04</date><risdate>2003</risdate><volume>22</volume><issue>38</issue><spage>5927</spage><epage>5937</epage><pages>5927-5937</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>The human Tousled-like kinases 1 and 2 (TLK) have been shown to be active during S phase of the cell cycle. TLK activity is rapidly suppressed by DNA damage and by inhibitors of replication. Here we report that the signal transduction pathway, which leads to transient suppression of TLK activity after the induction of double-strand breaks (DSBs) in the DNA, is dependent on the presence of a functional ataxia-telangiectasia-mutated kinase (ATM). Interestingly, we have discovered that rapid suppression of TLK activity after low doses of ultraviolet (UV) irradiation or aphidicolin-induced replication block is also ATM-dependent. The nature of the signal that triggers ATM-dependent downregulation of TLK activity after UVC and replication block remains unknown, but it is not due exclusively to DSBs in the DNA. We also demonstrate that TLK suppression is dependent on the presence of a functional Nijmegan Breakage Syndrome protein (NBS1). ATM-dependent phosphorylation of NBS1 is required for the suppression of TLK activity, indicating a role for NBS1 as an adaptor or scaffold in the ATM/TLK pathway. ATM does not phosphorylate TLK directly to regulate its activity, but Chk1 does phosphorylate TLK1 GST-fusion proteins
in vitro
. Using Chk1 siRNAs, we show that Chk1 is essential for the suppression of TLK activity after replication block, but that ATR, Chk2 and BRCA1 are dispensable for TLK suppression. Overall, we propose that ATM activation is not linked solely to DSBs and that ATM participates in initiating signaling pathways in response to replication block and UV-induced DNA damage.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>12955071</pmid><doi>10.1038/sj.onc.1206691</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncogene, 2003-09, Vol.22 (38), p.5927-5937 |
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| language | eng |
| recordid | cdi_proquest_miscellaneous_18826670 |
| source | MEDLINE; SpringerNature Journals; Nature Journals Online; EZB-FREE-00999 freely available EZB journals |
| subjects | Adaptor proteins Aphidicolin Aphidicolin - pharmacology Apoptosis Ataxia Ataxia Telangiectasia Mutated Proteins Biological and medical sciences BRCA1 protein Cell Biology Cell cycle Cell Cycle Proteins - drug effects Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Cycle Proteins - radiation effects Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cells, Cultured Checkpoint Kinase 1 CHK1 protein CHK2 protein Deoxyribonucleic acid Diverse techniques DNA DNA biosynthesis DNA damage DNA Damage - physiology DNA Replication - drug effects DNA Replication - radiation effects DNA-Binding Proteins Dose-Response Relationship, Radiation Enzyme Activation - drug effects Enzyme Activation - radiation effects Fundamental and applied biological sciences. Psychology Gamma Rays Glutathione Transferase - genetics Glutathione Transferase - metabolism Human Genetics Humans Internal Medicine Kinases Medicine Medicine & Public Health Molecular and cellular biology Nuclear Proteins - drug effects Nuclear Proteins - genetics Nuclear Proteins - metabolism Nuclear Proteins - radiation effects Oncology original-paper Phosphorylation Protein Kinases - drug effects Protein Kinases - genetics Protein Kinases - metabolism Protein Kinases - radiation effects Protein-Serine-Threonine Kinases - drug effects Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Protein-Serine-Threonine Kinases - radiation effects Proteins Radiation, Ionizing Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Replication RNA, Small Interfering - pharmacology S phase Serine - metabolism Signal transduction Signal Transduction - drug effects Signal Transduction - radiation effects siRNA Tumor Suppressor Proteins Ultraviolet Rays Yeast |
| title | Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T19%3A49%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Suppression%20of%20Tousled-like%20kinase%20activity%20after%20DNA%20damage%20or%20replication%20block%20requires%20ATM,%20NBS1%20and%20Chk1&rft.jtitle=Oncogene&rft.au=Krause,%20Darren%20R&rft.date=2003-09-04&rft.volume=22&rft.issue=38&rft.spage=5927&rft.epage=5937&rft.pages=5927-5937&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/sj.onc.1206691&rft_dat=%3Cgale_proqu%3EA189173937%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=227353488&rft_id=info:pmid/12955071&rft_galeid=A189173937&rfr_iscdi=true |