Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development
<p>Wee1 kinase regulates the G2/M cell cycle checkpoint by phosphorylating and inactivating the mitotic cyclin-dependent kinase 1 (Cdk1). Loss of Wee1 in many systems, including yeast and drosophila, leads to premature mitotic entry. However, the developmental role of Wee1 in mammals remains u...
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| Format: | Article |
| Language: | English |
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Ivyspring International Publisher
2006-01-01
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| Series: | International Journal of Biological Sciences |
| Online Access: | http://www.biolsci.org/v02p0161.htm |
| _version_ | 1828871139668000768 |
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| author | Yohei Tominaga, Cuiling Li, Rui-Hong Wang, Chu-Xia Deng |
| author_facet | Yohei Tominaga, Cuiling Li, Rui-Hong Wang, Chu-Xia Deng |
| author_sort | Yohei Tominaga, Cuiling Li, Rui-Hong Wang, Chu-Xia Deng |
| collection | DOAJ |
| description | <p>Wee1 kinase regulates the G2/M cell cycle checkpoint by phosphorylating and inactivating the mitotic cyclin-dependent kinase 1 (Cdk1). Loss of Wee1 in many systems, including yeast and drosophila, leads to premature mitotic entry. However, the developmental role of Wee1 in mammals remains unclear. In this study, we established Wee1 knockout mice by gene targeting. We found that <i>Wee<sup>-/-</sup></i> embryos were defective in the G2/M cell cycle checkpoint induced by γ-irradiation and died of apoptosis before embryonic (E) day 3.5. To study the function of Wee1 further, we have developed MEF cells in which Wee1 is disrupted by a tamoxifen inducible Cre-LoxP approach. We found that acute deletion of Wee1 resulted in profound growth defects and cell death. Wee1 deficient cells displayed chromosome aneuploidy and DNA damage as revealed by γ-H2AX foci formation and Chk2 activation. Further studies revealed a conserved mechanism of Wee1 in regulating mitotic entry and the G2/M checkpoint compared with other lower organisms. These data provide in vivo evidence that mammalian Wee1 plays a critical role in maintaining genome integrity and is essential for embryonic survival at the pre-implantation stage of mouse development.</p> |
| first_indexed | 2024-12-13T06:25:34Z |
| format | Article |
| id | doaj.art-27cebaec891542909b23f946e976623b |
| institution | Directory Open Access Journal |
| issn | 1449-2288 |
| language | English |
| last_indexed | 2024-12-13T06:25:34Z |
| publishDate | 2006-01-01 |
| publisher | Ivyspring International Publisher |
| record_format | Article |
| series | International Journal of Biological Sciences |
| spelling | doaj.art-27cebaec891542909b23f946e976623b2022-12-21T23:56:44ZengIvyspring International PublisherInternational Journal of Biological Sciences1449-22882006-01-0124161170Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic DevelopmentYohei Tominaga, Cuiling Li, Rui-Hong Wang, Chu-Xia Deng<p>Wee1 kinase regulates the G2/M cell cycle checkpoint by phosphorylating and inactivating the mitotic cyclin-dependent kinase 1 (Cdk1). Loss of Wee1 in many systems, including yeast and drosophila, leads to premature mitotic entry. However, the developmental role of Wee1 in mammals remains unclear. In this study, we established Wee1 knockout mice by gene targeting. We found that <i>Wee<sup>-/-</sup></i> embryos were defective in the G2/M cell cycle checkpoint induced by γ-irradiation and died of apoptosis before embryonic (E) day 3.5. To study the function of Wee1 further, we have developed MEF cells in which Wee1 is disrupted by a tamoxifen inducible Cre-LoxP approach. We found that acute deletion of Wee1 resulted in profound growth defects and cell death. Wee1 deficient cells displayed chromosome aneuploidy and DNA damage as revealed by γ-H2AX foci formation and Chk2 activation. Further studies revealed a conserved mechanism of Wee1 in regulating mitotic entry and the G2/M checkpoint compared with other lower organisms. These data provide in vivo evidence that mammalian Wee1 plays a critical role in maintaining genome integrity and is essential for embryonic survival at the pre-implantation stage of mouse development.</p>http://www.biolsci.org/v02p0161.htm |
| spellingShingle | Yohei Tominaga, Cuiling Li, Rui-Hong Wang, Chu-Xia Deng Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development International Journal of Biological Sciences |
| title | Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development |
| title_full | Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development |
| title_fullStr | Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development |
| title_full_unstemmed | Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development |
| title_short | Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development |
| title_sort | murine wee1 plays a critical role in cell cycle regulation and pre implantation stages of embryonic development |
| url | http://www.biolsci.org/v02p0161.htm |
| work_keys_str_mv | AT yoheitominagacuilingliruihongwangchuxiadeng murinewee1playsacriticalroleincellcycleregulationandpreimplantationstagesofembryonicdevelopment |