Molecular basis for the selective recognition and ubiquitination of centromeric histone H3 by yeast E3 ligase Psh1
doi: 10.1016/j.jgg.2021.04.007
Molecular basis for the selective recognition and ubiquitination of centromeric histone H3 by yeast E3 ligase Psh1
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摘要:
Centromeres are chromosomal loci marked by histone variant CenH3 (centromeric histone H3) and essential for genomic stability and cell division. The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast CenH3 (Cse4) for ubiquitination and controls the cellular level of Cse4 for proteolysis, but the underlying mechanism remains largely unknown. Here, we show that Psh1 uses a Cse4-binding domain (CBD, residues 1–211) to interact with Cse4-H4 instead of H3-H4, yielding a dissociation constant (Kd) of 27 nM. Psh1 recognizes Cse4-specific residues in the L1 loop and α2 helix to ensure Cse4 binding and ubiquitination. We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination. Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding. Together, our study reveals a novel Cse4-binding mode distinct from those of known CenH3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding.
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关键词:
- Cse4 /
- CENP-A /
- Psh1 /
- Scm3 /
- Selective recognition /
- Ubiquitination
Abstract:Centromeres are chromosomal loci marked by histone variant CenH3 (centromeric histone H3) and essential for genomic stability and cell division. The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast CenH3 (Cse4) for ubiquitination and controls the cellular level of Cse4 for proteolysis, but the underlying mechanism remains largely unknown. Here, we show that Psh1 uses a Cse4-binding domain (CBD, residues 1–211) to interact with Cse4-H4 instead of H3-H4, yielding a dissociation constant (Kd) of 27 nM. Psh1 recognizes Cse4-specific residues in the L1 loop and α2 helix to ensure Cse4 binding and ubiquitination. We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination. Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding. Together, our study reveals a novel Cse4-binding mode distinct from those of known CenH3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding.
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Key words:
- Cse4 /
- CENP-A /
- Psh1 /
- Scm3 /
- Selective recognition /
- Ubiquitination
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Amato, A., Schillaci, T., Lentini, L., Di Leonardo, A., 2009. CENPA overexpression promotes genome instability in pRb-depleted human cells. Mol. Cancer 8, 119. Au, W.-C., Crisp, M.J., DeLuca, S.Z., Rando, O.J., Basrai, M.A., 2008. Altered dosage and mislocalization of histone H3 and Cse4p lead to chromosome loss in Saccharomyces cerevisiae. Genetics 179, 263-275. Black, B.E., Foltz, D.R., Chakravarthy, S., Luger, K., Woods, V.L., Cleveland, D.W., 2004. Structural determinants for generating centromeric chromatin. Nature 430, 578-582. Black, B.E., Jansen, L.E.T., Maddox, P.S., Foltz, D.R., Desai, A.B., Shah, J.V., Cleveland, D.W., 2007. Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain. Mol. Cell 25, 309-322. Camahort, R., Li, B., Florens, L., Swanson, S.K., Washburn, M.P., Gerton, J.L., 2007. Scm3 is essential to recruit the histone h3 variant cse4 to centromeres and to maintain a functional kinetochore. Mol. Cell 26, 853-865. Camahort, R., Shivaraju, M., Mattingly, M., Li, B., Nakanishi, S., Zhu, D., Shilatifard, A., Workman, J.L., Gerton, J.L., 2009. Cse4 is part of an octameric nucleosome in budding yeast. Mol. Cell 35, 794-805. Earnshaw, W.C., Rothfield, N., 1985. Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma. Chromosoma 91, 313-321. Fachinetti, D., Logsdon, G.A., Abdullah, A., Selzer, E.B., Cleveland, D.W., Black, B.E., 2017. CENP-A modifications on Ser68 and Lys124 are dispensable for establishment, maintenance, and long-term function of human centromeres. Dev. Cell 40, 104-113. Fang, J., Liu, Y., Wei, Y., Deng, W., Yu, Z., Huang, L., Teng, Y., Yao, T., You, Q., Ruan, H., et al., 2015. Structural transitions of centromeric chromatin regulate the cell cycle-dependent recruitment of CENP-N. Genes Dev. 29, 1058-1073. Heun, P., Erhardt, S., Blower, M.D., Weiss, S., Skora, A.D., Karpen, G.H., 2006. Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev. Cell 10, 303-315. Hewawasam, G., Shivaraju, M., Mattingly, M., Venkatesh, S., Martin-Brown, S., Florens, L., Workman, J.L., Gerton, J.L., 2010. Psh1 is an E3 ubiquitin ligase that targets the centromeric histone variant Cse4. Mol. Cell 40, 444-454. Holland, A.J., Cleveland, D.W., 2009. Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat. Rev. Mol. Cell Biol. 10, 478-487. Lefrançois, P., Euskirchen, G.M., Auerbach, R.K., Rozowsky, J., Gibson, T., Yellman, C.M., Gerstein, M., Snyder, M., 2009. Efficient yeast ChIP-Seq using multiplex short-read DNA sequencing. BMC Genom. 10, 37. Maehara, K., Takahashi, K., Saitoh, S., 2010. CENP-A reduction induces a p53-dependent cellular senescence response to protect cells from executing defective mitoses. Mol. Cell Biol. 30, 2090-2104. Meluh, P.B., Yang, P., Glowczewski, L., Koshland, D., Smith, M.M., 1998. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell 94, 607-613. Niikura, Y., Kitagawa, R., Ogi, H., Abdulle, R., Pagala, V., Kitagawa, K., 2015. CENP-A K124 ubiquitylation is required for CENP-A deposition at the centromere. Dev. Cell 32, 589-603. Palmer, D.K., O'Day, K., Wener, M.H., Andrews, B.S., Margolis, R.L., 1987. A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones. J. Cell Biol. 104, 805-815. Ranjitkar, P., Press, M.O., Yi, X., Baker, R., MacCoss, M.J., Biggins, S., 2010. An E3 ubiquitin ligase prevents ectopic localization of the centromeric histone H3 variant via the centromere targeting domain. Mol. Cell 40, 455-464. Sanchez-Pulido, L., Pidoux, A.L., Ponting, C.P., Allshire, R.C., 2009. Common ancestry of the CENP-A chaperones Scm3 and HJURP. Cell 137, 1173-1174. Tomonaga, T., Matsushita, K., Yamaguchi, S., Oohashi, T., Shimada, H., Ochiai, T., Yoda, K., Nomura, F., 2003. Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer. Cancer Res. 63, 3511-3516. Van Hooser, A.A., Ouspenski, I.I., Gregson, H.C., Starr, D.A., Yen, T.J., Goldberg, M.L., Yokomori, K., Earnshaw, W.C., Sullivan, K.F., Brinkley, B.R., 2001. Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J. Cell Sci. 114, 3529-3542. Vermaak, D., Hayden, H.S., Henikoff, S., 2002. Centromere targeting element within the histone fold domain of Cid. Mol. Cell Biol. 22, 7553-7561. Zeitlin, S.G., Baker, N.M., Chapados, B.R., Soutoglou, E., Wang, J.Y.J., Berns, M.W., Cleveland, D.W., 2009. Double-strand DNA breaks recruit the centromeric histone CENP-A. Proc. Natl. Acad. Sci. U. S. A. 106, 15762-15767. Zhou, Z., Feng, H., Zhou, B.-R., Ghirlando, R., Hu, K., Zwolak, A., Miller Jenkins, L.M., Xiao, H., Tjandra, N., Wu, C., et al., 2011. Structural basis for recognition of centromere histone variant CenH3 by the chaperone Scm3. Nature 472, 234-237. -
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