Language
English
Publication Date
1-1-2026
Journal
The FEBS Journal
DOI
10.1111/febs.70240
PMID
40875546
PMCID
PMC12820605
PubMedCentral® Posted Date
8-28-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. Here we identify lysine demethylase 4A (KDM4A), an epigenetic 'eraser' of chromatin methyl marks, as a centrosome-localized protein, visualized at the nanometer-scale resolution. We additionally uncovered that KDM4A demethylase enzymatic activity is required to maintain centrosome homeostasis and integrity; a previously unknown functionality unlinked to altered expression of genes regulating centrosome number. We find that KDM4A interacts with and localizes to the centrosome in all stages of mitosis, where it maintains centrosome numbers and centriole engagement during mitosis. Loss of KDM4A results in supernumerary centrosomes and accrual of chromosome segregation errors including chromatin bridges and micronuclei, markers of genomic instability. In summary, these data highlight a previously unknown role for an epigenetic 'eraser' regulating centrosome integrity, mitotic fidelity, and genomic stability at the centrosome.
Keywords
Centrosome, Genomic Instability, Humans, Mitosis, Jumonji Domain-Containing Histone Demethylases, Chromosome Segregation, Chromatin, abnormal mitosis, centrosomes, genomic instability, KDM4A, mitosis
Published Open-Access
yes
Recommended Citation
Chowdhury, Pratim; Wang, Xiaoli; Han, Richard I; et al., "Lysine Demethylase 4A Is a Centrosome-Associated Protein Required for Centrosome Integrity and Genomic Stability" (2026). Faculty, Staff and Students Publications. 6439.
https://digitalcommons.library.tmc.edu/baylor_docs/6439