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Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing

Nucleosomes containing the histone H3 variant CENP-A are the epigenetic mark of centromeres, the kinetochore assembly sites required for chromosome segregation. HJURP is the CENP-A chaperone, which associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. How these pro...

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Autores principales: Pan, Dongqing, Walstein, Kai, Take, Annika, Bier, David, Kaiser, Nadine, Musacchio, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731319/
https://www.ncbi.nlm.nih.gov/pubmed/31492860
http://dx.doi.org/10.1038/s41467-019-12019-6
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author Pan, Dongqing
Walstein, Kai
Take, Annika
Bier, David
Kaiser, Nadine
Musacchio, Andrea
author_facet Pan, Dongqing
Walstein, Kai
Take, Annika
Bier, David
Kaiser, Nadine
Musacchio, Andrea
author_sort Pan, Dongqing
collection PubMed
description Nucleosomes containing the histone H3 variant CENP-A are the epigenetic mark of centromeres, the kinetochore assembly sites required for chromosome segregation. HJURP is the CENP-A chaperone, which associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. How these proteins interact to promote CENP-A deposition remains poorly understood. Here we show that two repeats in human HJURP proposed to be functionally distinct are in fact interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it. HJURP binds CENP-A:H4 dimers, and therefore assembly of CENP-A:H4 tetramers must be performed by two Mis18αβ:M18BP1:HJURP complexes, or by the same complex in consecutive rounds. The Mis18α N-terminal tails blockade two identical HJURP-repeat binding sites near the Mis18αβ C-terminal helices. These were identified by photo-cross-linking experiments and mutated to separate Mis18 from HJURP centromere recruitment. Our results identify molecular underpinnings of eukaryotic chromosome inheritance and shed light on how centromeres license CENP-A deposition.
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spelling pubmed-67313192019-09-09 Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing Pan, Dongqing Walstein, Kai Take, Annika Bier, David Kaiser, Nadine Musacchio, Andrea Nat Commun Article Nucleosomes containing the histone H3 variant CENP-A are the epigenetic mark of centromeres, the kinetochore assembly sites required for chromosome segregation. HJURP is the CENP-A chaperone, which associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. How these proteins interact to promote CENP-A deposition remains poorly understood. Here we show that two repeats in human HJURP proposed to be functionally distinct are in fact interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it. HJURP binds CENP-A:H4 dimers, and therefore assembly of CENP-A:H4 tetramers must be performed by two Mis18αβ:M18BP1:HJURP complexes, or by the same complex in consecutive rounds. The Mis18α N-terminal tails blockade two identical HJURP-repeat binding sites near the Mis18αβ C-terminal helices. These were identified by photo-cross-linking experiments and mutated to separate Mis18 from HJURP centromere recruitment. Our results identify molecular underpinnings of eukaryotic chromosome inheritance and shed light on how centromeres license CENP-A deposition. Nature Publishing Group UK 2019-09-06 /pmc/articles/PMC6731319/ /pubmed/31492860 http://dx.doi.org/10.1038/s41467-019-12019-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pan, Dongqing
Walstein, Kai
Take, Annika
Bier, David
Kaiser, Nadine
Musacchio, Andrea
Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
title Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
title_full Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
title_fullStr Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
title_full_unstemmed Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
title_short Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
title_sort mechanism of centromere recruitment of the cenp-a chaperone hjurp and its implications for centromere licensing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731319/
https://www.ncbi.nlm.nih.gov/pubmed/31492860
http://dx.doi.org/10.1038/s41467-019-12019-6
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