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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains. / Balachandra, Vinutha; Shrestha, Roshan L; Hammond, Colin M; Lin, Shinjen; Hendriks, Ivo A; Sethi, Subhash Chandra; Chen, Lu; Sevilla, Samantha; Caplen, Natasha J; Chari, Raj; Karpova, Tatiana S; McKinnon, Katherine; Todd, Matthew Am; Koparde, Vishal; Cheng, Ken Chih-Chien; Nielsen, Michael L; Groth, Anja; Basrai, Munira A.

In: The EMBO Journal, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Balachandra, V, Shrestha, RL, Hammond, CM, Lin, S, Hendriks, IA, Sethi, SC, Chen, L, Sevilla, S, Caplen, NJ, Chari, R, Karpova, TS, McKinnon, K, Todd, MA, Koparde, V, Cheng, KC-C, Nielsen, ML, Groth, A & Basrai, MA 2024, 'DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains', The EMBO Journal. https://doi.org/10.1038/s44318-024-00093-6

APA

Balachandra, V., Shrestha, R. L., Hammond, C. M., Lin, S., Hendriks, I. A., Sethi, S. C., Chen, L., Sevilla, S., Caplen, N. J., Chari, R., Karpova, T. S., McKinnon, K., Todd, M. A., Koparde, V., Cheng, K. C-C., Nielsen, M. L., Groth, A., & Basrai, M. A. (2024). DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains. The EMBO Journal. https://doi.org/10.1038/s44318-024-00093-6

Vancouver

Balachandra V, Shrestha RL, Hammond CM, Lin S, Hendriks IA, Sethi SC et al. DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains. The EMBO Journal. 2024. https://doi.org/10.1038/s44318-024-00093-6

Author

Balachandra, Vinutha ; Shrestha, Roshan L ; Hammond, Colin M ; Lin, Shinjen ; Hendriks, Ivo A ; Sethi, Subhash Chandra ; Chen, Lu ; Sevilla, Samantha ; Caplen, Natasha J ; Chari, Raj ; Karpova, Tatiana S ; McKinnon, Katherine ; Todd, Matthew Am ; Koparde, Vishal ; Cheng, Ken Chih-Chien ; Nielsen, Michael L ; Groth, Anja ; Basrai, Munira A. / DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains. In: The EMBO Journal. 2024.

Bibtex

@article{62ce5b66e90545ceb89fb3f9de47db8e,
title = "DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains",
abstract = "The centromeric histone H3 variant CENP-A is overexpressed in many cancers. The mislocalization of CENP-A to noncentromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. However, pathways that promote or prevent CENP-A mislocalization remain poorly defined. Here, we performed a genome-wide RNAi screen for regulators of CENP-A localization which identified DNAJC9, a J-domain protein implicated in histone H3-H4 protein folding, as a factor restricting CENP-A mislocalization. Cells lacking DNAJC9 exhibit mislocalization of CENP-A throughout the genome, and CIN phenotypes. Global interactome analysis showed that DNAJC9 depletion promotes the interaction of CENP-A with the DNA-replication-associated histone chaperone MCM2. CENP-A mislocalization upon DNAJC9 depletion was dependent on MCM2, defining MCM2 as a driver of CENP-A deposition at ectopic sites when H3-H4 supply chains are disrupted. Cells depleted for histone H3.3, also exhibit CENP-A mislocalization. In summary, we have defined novel factors that prevent mislocalization of CENP-A, and demonstrated that the integrity of H3-H4 supply chains regulated by histone chaperones such as DNAJC9 restrict CENP-A mislocalization and CIN.",
author = "Vinutha Balachandra and Shrestha, {Roshan L} and Hammond, {Colin M} and Shinjen Lin and Hendriks, {Ivo A} and Sethi, {Subhash Chandra} and Lu Chen and Samantha Sevilla and Caplen, {Natasha J} and Raj Chari and Karpova, {Tatiana S} and Katherine McKinnon and Todd, {Matthew Am} and Vishal Koparde and Cheng, {Ken Chih-Chien} and Nielsen, {Michael L} and Anja Groth and Basrai, {Munira A}",
note = "{\textcopyright} 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2024",
doi = "10.1038/s44318-024-00093-6",
language = "English",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains

AU - Balachandra, Vinutha

AU - Shrestha, Roshan L

AU - Hammond, Colin M

AU - Lin, Shinjen

AU - Hendriks, Ivo A

AU - Sethi, Subhash Chandra

AU - Chen, Lu

AU - Sevilla, Samantha

AU - Caplen, Natasha J

AU - Chari, Raj

AU - Karpova, Tatiana S

AU - McKinnon, Katherine

AU - Todd, Matthew Am

AU - Koparde, Vishal

AU - Cheng, Ken Chih-Chien

AU - Nielsen, Michael L

AU - Groth, Anja

AU - Basrai, Munira A

N1 - © 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

PY - 2024

Y1 - 2024

N2 - The centromeric histone H3 variant CENP-A is overexpressed in many cancers. The mislocalization of CENP-A to noncentromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. However, pathways that promote or prevent CENP-A mislocalization remain poorly defined. Here, we performed a genome-wide RNAi screen for regulators of CENP-A localization which identified DNAJC9, a J-domain protein implicated in histone H3-H4 protein folding, as a factor restricting CENP-A mislocalization. Cells lacking DNAJC9 exhibit mislocalization of CENP-A throughout the genome, and CIN phenotypes. Global interactome analysis showed that DNAJC9 depletion promotes the interaction of CENP-A with the DNA-replication-associated histone chaperone MCM2. CENP-A mislocalization upon DNAJC9 depletion was dependent on MCM2, defining MCM2 as a driver of CENP-A deposition at ectopic sites when H3-H4 supply chains are disrupted. Cells depleted for histone H3.3, also exhibit CENP-A mislocalization. In summary, we have defined novel factors that prevent mislocalization of CENP-A, and demonstrated that the integrity of H3-H4 supply chains regulated by histone chaperones such as DNAJC9 restrict CENP-A mislocalization and CIN.

AB - The centromeric histone H3 variant CENP-A is overexpressed in many cancers. The mislocalization of CENP-A to noncentromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. However, pathways that promote or prevent CENP-A mislocalization remain poorly defined. Here, we performed a genome-wide RNAi screen for regulators of CENP-A localization which identified DNAJC9, a J-domain protein implicated in histone H3-H4 protein folding, as a factor restricting CENP-A mislocalization. Cells lacking DNAJC9 exhibit mislocalization of CENP-A throughout the genome, and CIN phenotypes. Global interactome analysis showed that DNAJC9 depletion promotes the interaction of CENP-A with the DNA-replication-associated histone chaperone MCM2. CENP-A mislocalization upon DNAJC9 depletion was dependent on MCM2, defining MCM2 as a driver of CENP-A deposition at ectopic sites when H3-H4 supply chains are disrupted. Cells depleted for histone H3.3, also exhibit CENP-A mislocalization. In summary, we have defined novel factors that prevent mislocalization of CENP-A, and demonstrated that the integrity of H3-H4 supply chains regulated by histone chaperones such as DNAJC9 restrict CENP-A mislocalization and CIN.

U2 - 10.1038/s44318-024-00093-6

DO - 10.1038/s44318-024-00093-6

M3 - Journal article

C2 - 38600242

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

ER -

ID: 389361358