Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase
Summary: The cohesin- and condensin-related SMC5/6 complex has largely been studied in the context of DNA repair. Nevertheless, SMC5/6 has an undefined essential function even in the absence of cellular stress. Through the use of an auxin-inducible degradation system for rapidly depleting subunits o...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-04-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720304332 |
| _version_ | 1818923658905649152 |
|---|---|
| author | Andrés Bueno Venegas Toyoaki Natsume Masato Kanemaki Ian D. Hickson |
| author_facet | Andrés Bueno Venegas Toyoaki Natsume Masato Kanemaki Ian D. Hickson |
| author_sort | Andrés Bueno Venegas |
| collection | DOAJ |
| description | Summary: The cohesin- and condensin-related SMC5/6 complex has largely been studied in the context of DNA repair. Nevertheless, SMC5/6 has an undefined essential function even in the absence of cellular stress. Through the use of an auxin-inducible degradation system for rapidly depleting subunits of the SMC5/6 complex, we show that SMC5/6 is essential for viability in cancer-derived and normal human cells. Impairment of SMC5/6 function is associated with spontaneous induction of DNA damage, p53 activation, cell-cycle arrest, and senescence, as well as an increased frequency of various mitotic chromosome segregation abnormalities. However, we show that this chromosome missegregation is apparent only when SMC5/6 function is impaired during the preceding S and G2 phases. In contrast, degradation of SMC5/6 immediately prior to mitotic entry has little or no impact on the fidelity of chromosome segregation, highlighting the importance of the complex during interphase in order to ensure faithful sister chromatid disjunction. : Venegas et al. employ an auxin-inducible degron system for different subunits of the SMC5/6 complex to interrogate the short- and long-term effects of SMC5/6 impairment in human cells. Degradation of SMC5/6’s subunits at different cell cycle stages places the essential role of the complex during S phase. |
| first_indexed | 2024-12-20T02:12:56Z |
| format | Article |
| id | doaj.art-6c62816b70574c6aa94ddcba18d6af6a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T02:12:56Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6c62816b70574c6aa94ddcba18d6af6a2022-12-21T19:57:01ZengElsevierCell Reports2211-12472020-04-01313Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during InterphaseAndrés Bueno Venegas0Toyoaki Natsume1Masato Kanemaki2Ian D. Hickson3Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, 2200 Copenhagen N, DenmarkDivision of Molecular Cell Engineering, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan; Department of Genetics, SOKENDAI, Mishima, Shizuoka 411-8540, JapanDivision of Molecular Cell Engineering, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan; Department of Genetics, SOKENDAI, Mishima, Shizuoka 411-8540, JapanCenter for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, 2200 Copenhagen N, Denmark; Corresponding authorSummary: The cohesin- and condensin-related SMC5/6 complex has largely been studied in the context of DNA repair. Nevertheless, SMC5/6 has an undefined essential function even in the absence of cellular stress. Through the use of an auxin-inducible degradation system for rapidly depleting subunits of the SMC5/6 complex, we show that SMC5/6 is essential for viability in cancer-derived and normal human cells. Impairment of SMC5/6 function is associated with spontaneous induction of DNA damage, p53 activation, cell-cycle arrest, and senescence, as well as an increased frequency of various mitotic chromosome segregation abnormalities. However, we show that this chromosome missegregation is apparent only when SMC5/6 function is impaired during the preceding S and G2 phases. In contrast, degradation of SMC5/6 immediately prior to mitotic entry has little or no impact on the fidelity of chromosome segregation, highlighting the importance of the complex during interphase in order to ensure faithful sister chromatid disjunction. : Venegas et al. employ an auxin-inducible degron system for different subunits of the SMC5/6 complex to interrogate the short- and long-term effects of SMC5/6 impairment in human cells. Degradation of SMC5/6’s subunits at different cell cycle stages places the essential role of the complex during S phase.http://www.sciencedirect.com/science/article/pii/S2211124720304332 |
| spellingShingle | Andrés Bueno Venegas Toyoaki Natsume Masato Kanemaki Ian D. Hickson Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase Cell Reports |
| title | Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase |
| title_full | Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase |
| title_fullStr | Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase |
| title_full_unstemmed | Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase |
| title_short | Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase |
| title_sort | inducible degradation of the human smc5 6 complex reveals an essential role only during interphase |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720304332 |
| work_keys_str_mv | AT andresbuenovenegas inducibledegradationofthehumansmc56complexrevealsanessentialroleonlyduringinterphase AT toyoakinatsume inducibledegradationofthehumansmc56complexrevealsanessentialroleonlyduringinterphase AT masatokanemaki inducibledegradationofthehumansmc56complexrevealsanessentialroleonlyduringinterphase AT iandhickson inducibledegradationofthehumansmc56complexrevealsanessentialroleonlyduringinterphase |