The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint

During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gamete...
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Gespeichert in:

Autor*in:	Sara González-Arranz [verfasserIn] Isabel Acosta [verfasserIn] Jesús A. Carballo [verfasserIn] Beatriz Santos [verfasserIn] Pedro A. San-Segundo [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	meiosis meiotic recombination checkpoint Cdc5 polo kinase yeast

Übergeordnetes Werk:	In: Cells - MDPI AG, 2012, 10(2021), 10, p 2561
Übergeordnetes Werk:	volume:10 ; year:2021 ; number:10, p 2561

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cells10102561

Katalog-ID:	DOAJ077538587

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520			\|a During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control.
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allfields	10.3390/cells10102561 doi (DE-627)DOAJ077538587 (DE-599)DOAJ82f9a4d52ade499ca7e05057d9ac9056 DE-627 ger DE-627 rakwb eng QH573-671 Sara González-Arranz verfasserin aut The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control. meiosis meiotic recombination checkpoint Cdc5 polo kinase yeast Cytology Isabel Acosta verfasserin aut Jesús A. Carballo verfasserin aut Beatriz Santos verfasserin aut Pedro A. San-Segundo verfasserin aut In Cells MDPI AG, 2012 10(2021), 10, p 2561 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:10, p 2561 https://doi.org/10.3390/cells10102561 kostenfrei https://doaj.org/article/82f9a4d52ade499ca7e05057d9ac9056 kostenfrei https://www.mdpi.com/2073-4409/10/10/2561 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 10, p 2561
spelling	10.3390/cells10102561 doi (DE-627)DOAJ077538587 (DE-599)DOAJ82f9a4d52ade499ca7e05057d9ac9056 DE-627 ger DE-627 rakwb eng QH573-671 Sara González-Arranz verfasserin aut The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control. meiosis meiotic recombination checkpoint Cdc5 polo kinase yeast Cytology Isabel Acosta verfasserin aut Jesús A. Carballo verfasserin aut Beatriz Santos verfasserin aut Pedro A. San-Segundo verfasserin aut In Cells MDPI AG, 2012 10(2021), 10, p 2561 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:10, p 2561 https://doi.org/10.3390/cells10102561 kostenfrei https://doaj.org/article/82f9a4d52ade499ca7e05057d9ac9056 kostenfrei https://www.mdpi.com/2073-4409/10/10/2561 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 10, p 2561
allfields_unstemmed	10.3390/cells10102561 doi (DE-627)DOAJ077538587 (DE-599)DOAJ82f9a4d52ade499ca7e05057d9ac9056 DE-627 ger DE-627 rakwb eng QH573-671 Sara González-Arranz verfasserin aut The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control. meiosis meiotic recombination checkpoint Cdc5 polo kinase yeast Cytology Isabel Acosta verfasserin aut Jesús A. Carballo verfasserin aut Beatriz Santos verfasserin aut Pedro A. San-Segundo verfasserin aut In Cells MDPI AG, 2012 10(2021), 10, p 2561 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:10, p 2561 https://doi.org/10.3390/cells10102561 kostenfrei https://doaj.org/article/82f9a4d52ade499ca7e05057d9ac9056 kostenfrei https://www.mdpi.com/2073-4409/10/10/2561 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 10, p 2561
allfieldsGer	10.3390/cells10102561 doi (DE-627)DOAJ077538587 (DE-599)DOAJ82f9a4d52ade499ca7e05057d9ac9056 DE-627 ger DE-627 rakwb eng QH573-671 Sara González-Arranz verfasserin aut The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control. meiosis meiotic recombination checkpoint Cdc5 polo kinase yeast Cytology Isabel Acosta verfasserin aut Jesús A. Carballo verfasserin aut Beatriz Santos verfasserin aut Pedro A. San-Segundo verfasserin aut In Cells MDPI AG, 2012 10(2021), 10, p 2561 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:10, p 2561 https://doi.org/10.3390/cells10102561 kostenfrei https://doaj.org/article/82f9a4d52ade499ca7e05057d9ac9056 kostenfrei https://www.mdpi.com/2073-4409/10/10/2561 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 10, p 2561
allfieldsSound	10.3390/cells10102561 doi (DE-627)DOAJ077538587 (DE-599)DOAJ82f9a4d52ade499ca7e05057d9ac9056 DE-627 ger DE-627 rakwb eng QH573-671 Sara González-Arranz verfasserin aut The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control. meiosis meiotic recombination checkpoint Cdc5 polo kinase yeast Cytology Isabel Acosta verfasserin aut Jesús A. Carballo verfasserin aut Beatriz Santos verfasserin aut Pedro A. San-Segundo verfasserin aut In Cells MDPI AG, 2012 10(2021), 10, p 2561 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:10, p 2561 https://doi.org/10.3390/cells10102561 kostenfrei https://doaj.org/article/82f9a4d52ade499ca7e05057d9ac9056 kostenfrei https://www.mdpi.com/2073-4409/10/10/2561 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 10, p 2561
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authorswithroles_txt_mv	Sara González-Arranz @@aut@@ Isabel Acosta @@aut@@ Jesús A. Carballo @@aut@@ Beatriz Santos @@aut@@ Pedro A. San-Segundo @@aut@@
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callnumber-first	Q - Science
author	Sara González-Arranz
spellingShingle	Sara González-Arranz misc QH573-671 misc meiosis misc meiotic recombination checkpoint misc Cdc5 misc polo kinase misc yeast misc Cytology The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint
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topic_title	QH573-671 The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint meiosis meiotic recombination checkpoint Cdc5 polo kinase yeast
topic	misc QH573-671 misc meiosis misc meiotic recombination checkpoint misc Cdc5 misc polo kinase misc yeast misc Cytology
topic_unstemmed	misc QH573-671 misc meiosis misc meiotic recombination checkpoint misc Cdc5 misc polo kinase misc yeast misc Cytology
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title	The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint
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title_full	The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint
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author_browse	Sara González-Arranz Isabel Acosta Jesús A. Carballo Beatriz Santos Pedro A. San-Segundo
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title_sort	n-terminal region of the polo kinase cdc5 is required for downregulation of the meiotic recombination checkpoint
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title_auth	The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint
abstract	During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control.
abstractGer	During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control.
abstract_unstemmed	During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for <i<CDC5</i< gene expression. Previous work revealed that overexpression of <i<CDC5</i< partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective <i<zip1Δ</i< mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the <i<zip1Δ</i<-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the <i<zip1Δ</i< single mutant, the <i<zip1Δ cdc5-ΔN70</i< double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a <i<CDC5</i<-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control.
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title_short	The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint
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The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint

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