HJURP Antagonizes CENP-A Mislocalization Driven by the H3.3 Chaperones HIRA and DAXX

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Oct 27

PMID 30365520

Citations 29

Authors

Jonathan Nye

David Sturgill

Rajbir Athwal

Yamini Dalal

Affiliations

Soon will be listed here.

Abstract

The centromere specific histone H3 variant CENP-A/CENH3 specifies where the kinetochore is formed in most eukaryotes. Despite tight regulation of CENP-A levels in normal cells, overexpression of CENP-A is a feature shared by various types of solid tumors and results in its mislocalization to non-centromeric DNA. How CENP-A is assembled ectopically and the consequences of this mislocalization remain topics of high interest. Here, we report that in human colon cancer cells, the H3.3 chaperones HIRA and DAXX promote ectopic CENP-A deposition. Moreover, the correct balance between levels of the centromeric chaperone HJURP and CENP-A is essential to preclude ectopic assembly by H3.3 chaperones. In addition, we find that ectopic localization can recruit kinetochore components, and correlates with mitotic defects and DNA damage in G1 phase. Finally, CENP-A occupancy at the 8q24 locus is also correlated with amplification and overexpression of the MYC gene within that locus. Overall, these data provide insights into the causes and consequences of histone variant mislocalization in human cancer cells.

Citing Articles

Oncohistone H3 E97K mutation facilitates CENP-A mislocalization and chromosomal instability in budding yeast.

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The ortholog of human DNAJC9 promotes histone H3-H4 degradation and is counteracted by Asf1 in fission yeast.

Ding Y, Li J, Jiang H, Suo F, Shao G, Zhang X Nucleic Acids Res. 2025; 53(3).

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Native and tagged CENP-A histones are functionally inequivalent.

Bui M, Baek S, Bentahar R, Melters D, Dalal Y Epigenetics Chromatin. 2024; 17(1):19.

PMID: 38825690 PMC: 11145777. DOI: 10.1186/s13072-024-00543-9.

DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains.

Balachandra V, Shrestha R, Hammond C, Lin S, Hendriks I, Sethi S EMBO J. 2024; 43(11):2166-2197.

PMID: 38600242 PMC: 11148058. DOI: 10.1038/s44318-024-00093-6.

HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape.

Choi J, Kim T, Cho E Exp Mol Med. 2024; 56(2):251-263.

PMID: 38297159 PMC: 10907377. DOI: 10.1038/s12276-023-01145-3.

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