BRCA1 transports the DNA damage signal for CDDP‐induced centrosome amplification through the centrosomal Aurora A
Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage‐induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatme...
Gespeichert in:
| Veröffentlicht in: | Cancer science 2022-12, Vol.113 (12), p.4230-4243 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4243 |
|---|---|
| container_issue | 12 |
| container_start_page | 4230 |
| container_title | Cancer science |
| container_volume | 113 |
| creator | Qi, Huicheng Kikuchi, Megumi Yoshino, Yuki Fang, Zhenzhou Ohashi, Kazune Gotoh, Takato Ideta, Ryo Ui, Ayako Endo, Shino Otsuka, Kei Shindo, Norihisa Gonda, Kohsuke Ishioka, Chikashi Miki, Yoshio Iwabuchi, Tokuro Chiba, Natsuko |
| description | Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage‐induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S–G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo‐like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient‐derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP‐induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
BRCA1 is phosphorylated by ATM in the nucleus, moves to the cytoplasm, localizes to the centrosome, and promotes the centrosomal localization of Aurora A, which phosphorylates PLK1. Activated PLK1 causes premature centriole disengagement and centriole overduplication. |
| doi_str_mv | 10.1111/cas.15573 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9746055</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2753539632</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5333-85d21279f5937f98e10e1748dedad2f2cbbaa2dd130fcfb909990f82300472b13</originalsourceid><addsrcrecordid>eNp1kctu1DAUhi0EohdY8ALIEhu6SOtLHMcbpJApF6mCqi1ry_FlxlUSD3ZC1V0foc_Ik-DOlBEgcTY-kj99-nV-AF5hdIzznGiVjjFjnD4B-5iWouAIVU83Oy8EomQPHKR0jRCtSlE-B3u0QjWpCN4H6f1F22A4RTWmdYhTgtPKwsWXBho1qKWFyS9H1UMXImwXi_Ofd_d-NLO2Bmo7TjGkMFiohnXvnddq8mHMhhjm5Wpj2kHZ0cwxRAWbF-CZU32yLx_fQ_Dtw-lV-6k4-_rxc9ucFZpRSouaGYIJF44Jyp2oLUYW87I21ihDHNFdpxQxBlPktOsEEkIgVxOKUMlJh-kheLf1rudusGYTRfVyHf2g4q0Mysu_f0a_ksvwQwpeVoixLHj7KIjh-2zTJAeftO17NdowJ0k4JjXjJaEZffMPeh3mmC_3QDHKqKgoydTRltL5JilatwuDkXyoUuYq5abKzL7-M_2O_N1dBk62wI3v7e3_TbJtLrfKX6Q2qak</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2753539632</pqid></control><display><type>article</type><title>BRCA1 transports the DNA damage signal for CDDP‐induced centrosome amplification through the centrosomal Aurora A</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><creator>Qi, Huicheng ; Kikuchi, Megumi ; Yoshino, Yuki ; Fang, Zhenzhou ; Ohashi, Kazune ; Gotoh, Takato ; Ideta, Ryo ; Ui, Ayako ; Endo, Shino ; Otsuka, Kei ; Shindo, Norihisa ; Gonda, Kohsuke ; Ishioka, Chikashi ; Miki, Yoshio ; Iwabuchi, Tokuro ; Chiba, Natsuko</creator><creatorcontrib>Qi, Huicheng ; Kikuchi, Megumi ; Yoshino, Yuki ; Fang, Zhenzhou ; Ohashi, Kazune ; Gotoh, Takato ; Ideta, Ryo ; Ui, Ayako ; Endo, Shino ; Otsuka, Kei ; Shindo, Norihisa ; Gonda, Kohsuke ; Ishioka, Chikashi ; Miki, Yoshio ; Iwabuchi, Tokuro ; Chiba, Natsuko</creatorcontrib><description>Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage‐induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S–G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo‐like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient‐derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP‐induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
BRCA1 is phosphorylated by ATM in the nucleus, moves to the cytoplasm, localizes to the centrosome, and promotes the centrosomal localization of Aurora A, which phosphorylates PLK1. Activated PLK1 causes premature centriole disengagement and centriole overduplication.</description><identifier>ISSN: 1347-9032</identifier><identifier>ISSN: 1349-7006</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.15573</identifier><identifier>PMID: 36082621</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Antibodies ; Ataxia telangiectasia ; Ataxia telangiectasia mutated protein ; Aurora A ; Aurora Kinase A - metabolism ; BRCA1 ; BRCA1 protein ; BRCA1 Protein - genetics ; BRCA1 Protein - metabolism ; Breast cancer ; CDDP ; Cell cycle ; Cell Cycle - genetics ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; centrosome ; Centrosome - metabolism ; Cisplatin ; Cytoplasm ; Deoxyribonucleic acid ; DNA ; DNA Damage ; DNA repair ; Flow cytometry ; G2 Phase ; Humans ; Localization ; Nuclear transport ; Original ; ORIGINAL ARTICLES ; Phosphorylation ; Polo-like kinase 1 ; Proteins ; S phase ; Tumor suppressor genes ; Tumors</subject><ispartof>Cancer science, 2022-12, Vol.113 (12), p.4230-4243</ispartof><rights>2022 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2022. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5333-85d21279f5937f98e10e1748dedad2f2cbbaa2dd130fcfb909990f82300472b13</citedby><cites>FETCH-LOGICAL-c5333-85d21279f5937f98e10e1748dedad2f2cbbaa2dd130fcfb909990f82300472b13</cites><orcidid>0000-0001-6504-1290 ; 0000-0003-0029-3467 ; 0000-0002-3023-1227</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746055/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746055/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36082621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qi, Huicheng</creatorcontrib><creatorcontrib>Kikuchi, Megumi</creatorcontrib><creatorcontrib>Yoshino, Yuki</creatorcontrib><creatorcontrib>Fang, Zhenzhou</creatorcontrib><creatorcontrib>Ohashi, Kazune</creatorcontrib><creatorcontrib>Gotoh, Takato</creatorcontrib><creatorcontrib>Ideta, Ryo</creatorcontrib><creatorcontrib>Ui, Ayako</creatorcontrib><creatorcontrib>Endo, Shino</creatorcontrib><creatorcontrib>Otsuka, Kei</creatorcontrib><creatorcontrib>Shindo, Norihisa</creatorcontrib><creatorcontrib>Gonda, Kohsuke</creatorcontrib><creatorcontrib>Ishioka, Chikashi</creatorcontrib><creatorcontrib>Miki, Yoshio</creatorcontrib><creatorcontrib>Iwabuchi, Tokuro</creatorcontrib><creatorcontrib>Chiba, Natsuko</creatorcontrib><title>BRCA1 transports the DNA damage signal for CDDP‐induced centrosome amplification through the centrosomal Aurora A</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage‐induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S–G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo‐like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient‐derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP‐induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
BRCA1 is phosphorylated by ATM in the nucleus, moves to the cytoplasm, localizes to the centrosome, and promotes the centrosomal localization of Aurora A, which phosphorylates PLK1. Activated PLK1 causes premature centriole disengagement and centriole overduplication.</description><subject>Antibodies</subject><subject>Ataxia telangiectasia</subject><subject>Ataxia telangiectasia mutated protein</subject><subject>Aurora A</subject><subject>Aurora Kinase A - metabolism</subject><subject>BRCA1</subject><subject>BRCA1 protein</subject><subject>BRCA1 Protein - genetics</subject><subject>BRCA1 Protein - metabolism</subject><subject>Breast cancer</subject><subject>CDDP</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>centrosome</subject><subject>Centrosome - metabolism</subject><subject>Cisplatin</subject><subject>Cytoplasm</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA repair</subject><subject>Flow cytometry</subject><subject>G2 Phase</subject><subject>Humans</subject><subject>Localization</subject><subject>Nuclear transport</subject><subject>Original</subject><subject>ORIGINAL ARTICLES</subject><subject>Phosphorylation</subject><subject>Polo-like kinase 1</subject><subject>Proteins</subject><subject>S phase</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kctu1DAUhi0EohdY8ALIEhu6SOtLHMcbpJApF6mCqi1ry_FlxlUSD3ZC1V0foc_Ik-DOlBEgcTY-kj99-nV-AF5hdIzznGiVjjFjnD4B-5iWouAIVU83Oy8EomQPHKR0jRCtSlE-B3u0QjWpCN4H6f1F22A4RTWmdYhTgtPKwsWXBho1qKWFyS9H1UMXImwXi_Ofd_d-NLO2Bmo7TjGkMFiohnXvnddq8mHMhhjm5Wpj2kHZ0cwxRAWbF-CZU32yLx_fQ_Dtw-lV-6k4-_rxc9ucFZpRSouaGYIJF44Jyp2oLUYW87I21ihDHNFdpxQxBlPktOsEEkIgVxOKUMlJh-kheLf1rudusGYTRfVyHf2g4q0Mysu_f0a_ksvwQwpeVoixLHj7KIjh-2zTJAeftO17NdowJ0k4JjXjJaEZffMPeh3mmC_3QDHKqKgoydTRltL5JilatwuDkXyoUuYq5abKzL7-M_2O_N1dBk62wI3v7e3_TbJtLrfKX6Q2qak</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Qi, Huicheng</creator><creator>Kikuchi, Megumi</creator><creator>Yoshino, Yuki</creator><creator>Fang, Zhenzhou</creator><creator>Ohashi, Kazune</creator><creator>Gotoh, Takato</creator><creator>Ideta, Ryo</creator><creator>Ui, Ayako</creator><creator>Endo, Shino</creator><creator>Otsuka, Kei</creator><creator>Shindo, Norihisa</creator><creator>Gonda, Kohsuke</creator><creator>Ishioka, Chikashi</creator><creator>Miki, Yoshio</creator><creator>Iwabuchi, Tokuro</creator><creator>Chiba, Natsuko</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6504-1290</orcidid><orcidid>https://orcid.org/0000-0003-0029-3467</orcidid><orcidid>https://orcid.org/0000-0002-3023-1227</orcidid></search><sort><creationdate>202212</creationdate><title>BRCA1 transports the DNA damage signal for CDDP‐induced centrosome amplification through the centrosomal Aurora A</title><author>Qi, Huicheng ; Kikuchi, Megumi ; Yoshino, Yuki ; Fang, Zhenzhou ; Ohashi, Kazune ; Gotoh, Takato ; Ideta, Ryo ; Ui, Ayako ; Endo, Shino ; Otsuka, Kei ; Shindo, Norihisa ; Gonda, Kohsuke ; Ishioka, Chikashi ; Miki, Yoshio ; Iwabuchi, Tokuro ; Chiba, Natsuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5333-85d21279f5937f98e10e1748dedad2f2cbbaa2dd130fcfb909990f82300472b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies</topic><topic>Ataxia telangiectasia</topic><topic>Ataxia telangiectasia mutated protein</topic><topic>Aurora A</topic><topic>Aurora Kinase A - metabolism</topic><topic>BRCA1</topic><topic>BRCA1 protein</topic><topic>BRCA1 Protein - genetics</topic><topic>BRCA1 Protein - metabolism</topic><topic>Breast cancer</topic><topic>CDDP</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>centrosome</topic><topic>Centrosome - metabolism</topic><topic>Cisplatin</topic><topic>Cytoplasm</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>DNA repair</topic><topic>Flow cytometry</topic><topic>G2 Phase</topic><topic>Humans</topic><topic>Localization</topic><topic>Nuclear transport</topic><topic>Original</topic><topic>ORIGINAL ARTICLES</topic><topic>Phosphorylation</topic><topic>Polo-like kinase 1</topic><topic>Proteins</topic><topic>S phase</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Huicheng</creatorcontrib><creatorcontrib>Kikuchi, Megumi</creatorcontrib><creatorcontrib>Yoshino, Yuki</creatorcontrib><creatorcontrib>Fang, Zhenzhou</creatorcontrib><creatorcontrib>Ohashi, Kazune</creatorcontrib><creatorcontrib>Gotoh, Takato</creatorcontrib><creatorcontrib>Ideta, Ryo</creatorcontrib><creatorcontrib>Ui, Ayako</creatorcontrib><creatorcontrib>Endo, Shino</creatorcontrib><creatorcontrib>Otsuka, Kei</creatorcontrib><creatorcontrib>Shindo, Norihisa</creatorcontrib><creatorcontrib>Gonda, Kohsuke</creatorcontrib><creatorcontrib>Ishioka, Chikashi</creatorcontrib><creatorcontrib>Miki, Yoshio</creatorcontrib><creatorcontrib>Iwabuchi, Tokuro</creatorcontrib><creatorcontrib>Chiba, Natsuko</creatorcontrib><collection>Wiley Online Library 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>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qi, Huicheng</au><au>Kikuchi, Megumi</au><au>Yoshino, Yuki</au><au>Fang, Zhenzhou</au><au>Ohashi, Kazune</au><au>Gotoh, Takato</au><au>Ideta, Ryo</au><au>Ui, Ayako</au><au>Endo, Shino</au><au>Otsuka, Kei</au><au>Shindo, Norihisa</au><au>Gonda, Kohsuke</au><au>Ishioka, Chikashi</au><au>Miki, Yoshio</au><au>Iwabuchi, Tokuro</au><au>Chiba, Natsuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BRCA1 transports the DNA damage signal for CDDP‐induced centrosome amplification through the centrosomal Aurora A</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2022-12</date><risdate>2022</risdate><volume>113</volume><issue>12</issue><spage>4230</spage><epage>4243</epage><pages>4230-4243</pages><issn>1347-9032</issn><issn>1349-7006</issn><eissn>1349-7006</eissn><abstract>Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage‐induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S–G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo‐like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient‐derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP‐induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
BRCA1 is phosphorylated by ATM in the nucleus, moves to the cytoplasm, localizes to the centrosome, and promotes the centrosomal localization of Aurora A, which phosphorylates PLK1. Activated PLK1 causes premature centriole disengagement and centriole overduplication.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>36082621</pmid><doi>10.1111/cas.15573</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-6504-1290</orcidid><orcidid>https://orcid.org/0000-0003-0029-3467</orcidid><orcidid>https://orcid.org/0000-0002-3023-1227</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1347-9032 |
| ispartof | Cancer science, 2022-12, Vol.113 (12), p.4230-4243 |
| issn | 1347-9032 1349-7006 1349-7006 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9746055 |
| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; PubMed Central |
| subjects | Antibodies Ataxia telangiectasia Ataxia telangiectasia mutated protein Aurora A Aurora Kinase A - metabolism BRCA1 BRCA1 protein BRCA1 Protein - genetics BRCA1 Protein - metabolism Breast cancer CDDP Cell cycle Cell Cycle - genetics Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism centrosome Centrosome - metabolism Cisplatin Cytoplasm Deoxyribonucleic acid DNA DNA Damage DNA repair Flow cytometry G2 Phase Humans Localization Nuclear transport Original ORIGINAL ARTICLES Phosphorylation Polo-like kinase 1 Proteins S phase Tumor suppressor genes Tumors |
| title | BRCA1 transports the DNA damage signal for CDDP‐induced centrosome amplification through the centrosomal Aurora A |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T13%3A35%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=BRCA1%20transports%20the%20DNA%20damage%20signal%20for%20CDDP%E2%80%90induced%20centrosome%20amplification%20through%20the%20centrosomal%20Aurora%20A&rft.jtitle=Cancer%20science&rft.au=Qi,%20Huicheng&rft.date=2022-12&rft.volume=113&rft.issue=12&rft.spage=4230&rft.epage=4243&rft.pages=4230-4243&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.15573&rft_dat=%3Cproquest_pubme%3E2753539632%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2753539632&rft_id=info:pmid/36082621&rfr_iscdi=true |