SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination
Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumula...
Gespeichert in:
| Veröffentlicht in: | Nucleic acids research 2022-05, Vol.50 (9), p.5129-5144 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5144 |
|---|---|
| container_issue | 9 |
| container_start_page | 5129 |
| container_title | Nucleic acids research |
| container_volume | 50 |
| creator | Guan, Yongjuan Lin, Huijuan Leu, N Adrian Ruthel, Gordon Fuchs, Serge Y Busino, Luca Luo, Mengcheng Wang, P Jeremy |
| description | Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis. |
| doi_str_mv | 10.1093/nar/gkac304 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9122608</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2658229002</sourcerecordid><originalsourceid>FETCH-LOGICAL-c381t-3afe01e184e265cde87d2316d420b74f1911157d84242322c312846e988f88513</originalsourceid><addsrcrecordid>eNpVkb1PwzAQxS0EouVjYkcekVCoz3ZSZ0FC5VOqYAAGJstxLsU0icFOkPrfE9SCYLrhfvfu6T1CjoCdAcvFpDVhslgaK5jcImMQGU9knvFtMmaCpQkwqUZkL8Y3xkBCKnfJSKRS5WwKY_LyOLumfeE-ete5ll4JWruFiUgDLvradBjp5f0FLX1f1JjELpi2pEVAs4x04NGEekUbdL5zdrixvilcazrn2wOyU5k64uFm7pPn66un2W0yf7i5m13MEysUdIkwFTJAUBJ5ltoS1bTkArJSclZMZQU5AKTTUkkuueDcCuBKZpgrVSmVgtgn52vd975osLTYDiZr_R5cY8JKe-P0_03rXvXCf-ocOM-YGgRONgLBf_QYO924aLGuTYu-j3qwpTjPGeMDerpGbfAxBqx-3wDT32XooQy9KWOgj_86-2V_0hdfGMOGQQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2658229002</pqid></control><display><type>article</type><title>SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Access via Oxford University Press (Open Access Collection)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Guan, Yongjuan ; Lin, Huijuan ; Leu, N Adrian ; Ruthel, Gordon ; Fuchs, Serge Y ; Busino, Luca ; Luo, Mengcheng ; Wang, P Jeremy</creator><creatorcontrib>Guan, Yongjuan ; Lin, Huijuan ; Leu, N Adrian ; Ruthel, Gordon ; Fuchs, Serge Y ; Busino, Luca ; Luo, Mengcheng ; Wang, P Jeremy</creatorcontrib><description>Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis.</description><identifier>ISSN: 0305-1048</identifier><identifier>ISSN: 1362-4962</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkac304</identifier><identifier>PMID: 35489071</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Cell Cycle Proteins - metabolism ; DNA ; DNA Breaks, Double-Stranded ; Female ; Genome Integrity, Repair and ; HEK293 Cells ; Homologous Recombination ; Humans ; Male ; Meiosis - genetics ; SKP Cullin F-Box Protein Ligases - genetics ; Transcription Factors - genetics ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism ; Ubiquitins - genetics</subject><ispartof>Nucleic acids research, 2022-05, Vol.50 (9), p.5129-5144</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-3afe01e184e265cde87d2316d420b74f1911157d84242322c312846e988f88513</citedby><cites>FETCH-LOGICAL-c381t-3afe01e184e265cde87d2316d420b74f1911157d84242322c312846e988f88513</cites><orcidid>0000-0002-0136-5103 ; 0000-0001-7058-5911 ; 0000-0003-2311-4089</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/PMC9122608/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122608/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35489071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guan, Yongjuan</creatorcontrib><creatorcontrib>Lin, Huijuan</creatorcontrib><creatorcontrib>Leu, N Adrian</creatorcontrib><creatorcontrib>Ruthel, Gordon</creatorcontrib><creatorcontrib>Fuchs, Serge Y</creatorcontrib><creatorcontrib>Busino, Luca</creatorcontrib><creatorcontrib>Luo, Mengcheng</creatorcontrib><creatorcontrib>Wang, P Jeremy</creatorcontrib><title>SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis.</description><subject>Cell Cycle Proteins - metabolism</subject><subject>DNA</subject><subject>DNA Breaks, Double-Stranded</subject><subject>Female</subject><subject>Genome Integrity, Repair and</subject><subject>HEK293 Cells</subject><subject>Homologous Recombination</subject><subject>Humans</subject><subject>Male</subject><subject>Meiosis - genetics</subject><subject>SKP Cullin F-Box Protein Ligases - genetics</subject><subject>Transcription Factors - genetics</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Ubiquitins - genetics</subject><issn>0305-1048</issn><issn>1362-4962</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkb1PwzAQxS0EouVjYkcekVCoz3ZSZ0FC5VOqYAAGJstxLsU0icFOkPrfE9SCYLrhfvfu6T1CjoCdAcvFpDVhslgaK5jcImMQGU9knvFtMmaCpQkwqUZkL8Y3xkBCKnfJSKRS5WwKY_LyOLumfeE-ete5ll4JWruFiUgDLvradBjp5f0FLX1f1JjELpi2pEVAs4x04NGEekUbdL5zdrixvilcazrn2wOyU5k64uFm7pPn66un2W0yf7i5m13MEysUdIkwFTJAUBJ5ltoS1bTkArJSclZMZQU5AKTTUkkuueDcCuBKZpgrVSmVgtgn52vd975osLTYDiZr_R5cY8JKe-P0_03rXvXCf-ocOM-YGgRONgLBf_QYO924aLGuTYu-j3qwpTjPGeMDerpGbfAxBqx-3wDT32XooQy9KWOgj_86-2V_0hdfGMOGQQ</recordid><startdate>20220520</startdate><enddate>20220520</enddate><creator>Guan, Yongjuan</creator><creator>Lin, Huijuan</creator><creator>Leu, N Adrian</creator><creator>Ruthel, Gordon</creator><creator>Fuchs, Serge Y</creator><creator>Busino, Luca</creator><creator>Luo, Mengcheng</creator><creator>Wang, P Jeremy</creator><general>Oxford University Press</general><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><orcidid>https://orcid.org/0000-0002-0136-5103</orcidid><orcidid>https://orcid.org/0000-0001-7058-5911</orcidid><orcidid>https://orcid.org/0000-0003-2311-4089</orcidid></search><sort><creationdate>20220520</creationdate><title>SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination</title><author>Guan, Yongjuan ; Lin, Huijuan ; Leu, N Adrian ; Ruthel, Gordon ; Fuchs, Serge Y ; Busino, Luca ; Luo, Mengcheng ; Wang, P Jeremy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-3afe01e184e265cde87d2316d420b74f1911157d84242322c312846e988f88513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Cell Cycle Proteins - metabolism</topic><topic>DNA</topic><topic>DNA Breaks, Double-Stranded</topic><topic>Female</topic><topic>Genome Integrity, Repair and</topic><topic>HEK293 Cells</topic><topic>Homologous Recombination</topic><topic>Humans</topic><topic>Male</topic><topic>Meiosis - genetics</topic><topic>SKP Cullin F-Box Protein Ligases - genetics</topic><topic>Transcription Factors - genetics</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><topic>Ubiquitins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guan, Yongjuan</creatorcontrib><creatorcontrib>Lin, Huijuan</creatorcontrib><creatorcontrib>Leu, N Adrian</creatorcontrib><creatorcontrib>Ruthel, Gordon</creatorcontrib><creatorcontrib>Fuchs, Serge Y</creatorcontrib><creatorcontrib>Busino, Luca</creatorcontrib><creatorcontrib>Luo, Mengcheng</creatorcontrib><creatorcontrib>Wang, P Jeremy</creatorcontrib><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>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guan, Yongjuan</au><au>Lin, Huijuan</au><au>Leu, N Adrian</au><au>Ruthel, Gordon</au><au>Fuchs, Serge Y</au><au>Busino, Luca</au><au>Luo, Mengcheng</au><au>Wang, P Jeremy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2022-05-20</date><risdate>2022</risdate><volume>50</volume><issue>9</issue><spage>5129</spage><epage>5144</epage><pages>5129-5144</pages><issn>0305-1048</issn><issn>1362-4962</issn><eissn>1362-4962</eissn><abstract>Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>35489071</pmid><doi>10.1093/nar/gkac304</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-0136-5103</orcidid><orcidid>https://orcid.org/0000-0001-7058-5911</orcidid><orcidid>https://orcid.org/0000-0003-2311-4089</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0305-1048 |
| ispartof | Nucleic acids research, 2022-05, Vol.50 (9), p.5129-5144 |
| issn | 0305-1048 1362-4962 1362-4962 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9122608 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Access via Oxford University Press (Open Access Collection); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Cell Cycle Proteins - metabolism DNA DNA Breaks, Double-Stranded Female Genome Integrity, Repair and HEK293 Cells Homologous Recombination Humans Male Meiosis - genetics SKP Cullin F-Box Protein Ligases - genetics Transcription Factors - genetics Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitins - genetics |
| title | SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T19%3A20%3A23IST&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=SCF%20ubiquitin%20E3%20ligase%20regulates%20DNA%20double-strand%20breaks%20in%20early%20meiotic%20recombination&rft.jtitle=Nucleic%20acids%20research&rft.au=Guan,%20Yongjuan&rft.date=2022-05-20&rft.volume=50&rft.issue=9&rft.spage=5129&rft.epage=5144&rft.pages=5129-5144&rft.issn=0305-1048&rft.eissn=1362-4962&rft_id=info:doi/10.1093/nar/gkac304&rft_dat=%3Cproquest_pubme%3E2658229002%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=2658229002&rft_id=info:pmid/35489071&rfr_iscdi=true |