The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes

Mérai Z, Chumak N, García-Aguilar M, Hsieh T-F, Nishimura T, Schoft VK, Bindics J, Ślusarz L, Arnoux S, Opravil S, Mechtler K, ZILBERMAN D, Fischer RL, Tamaru H. 2014. The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes. Proceedings of the National Academy of Sciences. 111(45), 16166–16171.


Journal Article | Published | English

Scopus indexed
Author
Mérai, Zsuzsanna; Chumak, Nina; García-Aguilar, Marcelina; Hsieh, Tzung-Fu; Nishimura, Toshiro; Schoft, Vera K.; Bindics, János; Ślusarz, Lucyna; Arnoux, Stéphanie; Opravil, Susanne; Mechtler, Karl; ZILBERMAN, DanielIST Austria
All
Abstract
Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved AAA-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48ANPL4 complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction.
Publishing Year
Date Published
2014-11-11
Journal Title
Proceedings of the National Academy of Sciences
Volume
111
Issue
45
Page
16166-16171
ISSN
eISSN
IST-REx-ID

Cite this

Mérai Z, Chumak N, García-Aguilar M, et al. The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes. Proceedings of the National Academy of Sciences. 2014;111(45):16166-16171. doi:10.1073/pnas.1418564111
Mérai, Z., Chumak, N., García-Aguilar, M., Hsieh, T.-F., Nishimura, T., Schoft, V. K., … Tamaru, H. (2014). The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1418564111
Mérai, Zsuzsanna, Nina Chumak, Marcelina García-Aguilar, Tzung-Fu Hsieh, Toshiro Nishimura, Vera K. Schoft, János Bindics, et al. “The AAA-ATPase Molecular Chaperone Cdc48/P97 Disassembles Sumoylated Centromeres, Decondenses Heterochromatin, and Activates Ribosomal RNA Genes.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2014. https://doi.org/10.1073/pnas.1418564111.
Z. Mérai et al., “The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes,” Proceedings of the National Academy of Sciences, vol. 111, no. 45. National Academy of Sciences, pp. 16166–16171, 2014.
Mérai Z, Chumak N, García-Aguilar M, Hsieh T-F, Nishimura T, Schoft VK, Bindics J, Ślusarz L, Arnoux S, Opravil S, Mechtler K, ZILBERMAN D, Fischer RL, Tamaru H. 2014. The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes. Proceedings of the National Academy of Sciences. 111(45), 16166–16171.
Mérai, Zsuzsanna, et al. “The AAA-ATPase Molecular Chaperone Cdc48/P97 Disassembles Sumoylated Centromeres, Decondenses Heterochromatin, and Activates Ribosomal RNA Genes.” Proceedings of the National Academy of Sciences, vol. 111, no. 45, National Academy of Sciences, 2014, pp. 16166–71, doi:10.1073/pnas.1418564111.
All files available under the following license(s):
Copyright Statement:
This Item is protected by copyright and/or related rights. [...]

Link(s) to Main File(s)
Access Level
OA Open Access

Export

Marked Publications

Open Data IST Research Explorer

Sources

PMID: 25344531
PubMed | Europe PMC

Search this title in

Google Scholar