Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events

The proper regulation of cell cycle transitions is paramount to the maintenance of cellular genome integrity. In Saccharomyces cerevisiae, the mitotic exit network (MEN) is a Ras-like signaling cascade that effects the transition from M phase to G1 during the cell division cycle in budding yeast. ME...

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Main Authors: Jenna Whalen, Courtney Sniffen, Siobhan Gartland, Michael Vannini, Anupama Seshan
Format: Article
Language:English
Published: Oxford University Press 2018-11-01
Series:G3: Genes, Genomes, Genetics
Subjects:
Online Access:http://g3journal.org/lookup/doi/10.1534/g3.118.200672
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author Jenna Whalen
Courtney Sniffen
Siobhan Gartland
Michael Vannini
Anupama Seshan
author_facet Jenna Whalen
Courtney Sniffen
Siobhan Gartland
Michael Vannini
Anupama Seshan
author_sort Jenna Whalen
collection DOAJ
description The proper regulation of cell cycle transitions is paramount to the maintenance of cellular genome integrity. In Saccharomyces cerevisiae, the mitotic exit network (MEN) is a Ras-like signaling cascade that effects the transition from M phase to G1 during the cell division cycle in budding yeast. MEN activation is tightly regulated. It occurs during anaphase and is coupled to mitotic spindle position by the spindle position checkpoint (SPoC). Bfa1 is a key component of the SPoC and functions as part of a two-component GAP complex along with Bub2. The GAP activity of Bfa1-Bub2 keeps the MEN GTPase Tem1 inactive in cells with mispositioned spindles, thereby preventing inappropriate mitotic exit and preserving genome integrity. Interestingly, a GAP-independent role for Bfa1 in mitotic exit regulation has been previously identified. However the nature of this Bub2-independent role and its biological significance are not understood. Here we show that Bfa1 also activates the MEN by promoting the localization of Tem1 primarily to the daughter spindle pole body (dSPB). We demonstrate that the overexpression of BFA1 is lethal due to defects in Tem1 localization, which is required for its activity. In addition, our studies demonstrate a Tem1-independent role for Bfa1 in promoting proper cytokinesis. Cells lacking TEM1, in which the essential mitotic exit function is bypassed, exhibit cytokinesis defects. These defects are suppressed by the overexpression of BFA1. We conclude that Bfa1 functions to both inhibit and activate late mitotic events.
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spelling doaj.art-a1d33738ddb6436c92719cacc135d9442022-12-21T20:25:28ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362018-11-018113397341010.1534/g3.118.2006722Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic EventsJenna WhalenCourtney SniffenSiobhan GartlandMichael VanniniAnupama SeshanThe proper regulation of cell cycle transitions is paramount to the maintenance of cellular genome integrity. In Saccharomyces cerevisiae, the mitotic exit network (MEN) is a Ras-like signaling cascade that effects the transition from M phase to G1 during the cell division cycle in budding yeast. MEN activation is tightly regulated. It occurs during anaphase and is coupled to mitotic spindle position by the spindle position checkpoint (SPoC). Bfa1 is a key component of the SPoC and functions as part of a two-component GAP complex along with Bub2. The GAP activity of Bfa1-Bub2 keeps the MEN GTPase Tem1 inactive in cells with mispositioned spindles, thereby preventing inappropriate mitotic exit and preserving genome integrity. Interestingly, a GAP-independent role for Bfa1 in mitotic exit regulation has been previously identified. However the nature of this Bub2-independent role and its biological significance are not understood. Here we show that Bfa1 also activates the MEN by promoting the localization of Tem1 primarily to the daughter spindle pole body (dSPB). We demonstrate that the overexpression of BFA1 is lethal due to defects in Tem1 localization, which is required for its activity. In addition, our studies demonstrate a Tem1-independent role for Bfa1 in promoting proper cytokinesis. Cells lacking TEM1, in which the essential mitotic exit function is bypassed, exhibit cytokinesis defects. These defects are suppressed by the overexpression of BFA1. We conclude that Bfa1 functions to both inhibit and activate late mitotic events.http://g3journal.org/lookup/doi/10.1534/g3.118.200672Bfa1Tem1MENmitotic exitcytokinesis
spellingShingle Jenna Whalen
Courtney Sniffen
Siobhan Gartland
Michael Vannini
Anupama Seshan
Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events
G3: Genes, Genomes, Genetics
Bfa1
Tem1
MEN
mitotic exit
cytokinesis
title Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events
title_full Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events
title_fullStr Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events
title_full_unstemmed Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events
title_short Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events
title_sort budding yeast bfa1 has multiple positive roles in directing late mitotic events
topic Bfa1
Tem1
MEN
mitotic exit
cytokinesis
url http://g3journal.org/lookup/doi/10.1534/g3.118.200672
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AT siobhangartland buddingyeastbfa1hasmultiplepositiverolesindirectinglatemitoticevents
AT michaelvannini buddingyeastbfa1hasmultiplepositiverolesindirectinglatemitoticevents
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