PBRM1 directs PBAF to pericentromeres and protects centromere integrity

The specialised structure of the centromere is critical for effective chromosome segregation, but its repetitive nature makes it vulnerable to rearrangements. Centromere fragility can drive tumorigenesis, but protective mechanisms preventing fragility are still not fully understood. The PBAF chromatin remodelling complex is frequently misregulated in cancer, but its role in cancer is incompletely characterized. Here, we identify PBAF as a protector of centromere and pericentromere structure with profound consequences for genome stability. A conserved feature of isogenic cell lines lacking PBRM1, a subunit of PBAF, is compromised centromere and pericentromere integrity. PBAF is present at these regions, and binding patterns of PBAF and H3K9 methylation change when PBRM1 is absent. PBRM1 loss creates a dependence on the spindle assembly checkpoint, which represents a therapeutic vulnerability. Importantly, we find that even in the absence of any perturbations, PBRM1 loss leads to centromere fragility, thus identifying a key player in centromere protection.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-02-26
DOI
https://doi.org/10.1038/s41467-025-57277-9
Citations
8
Primary Topic
Chromosomal and Genetic Variations
Type
article
Field-Weighted Citation Impact
14.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

PBRM1 directs PBAF to pericentromeres and protects centromere integrity

Karen A. Lane, Najaf Amin, Jessica A. Downs, Frank T. Zenke et al.
8 citations
Nature Communications
Chromosomal and Genetic Variations
14.00
article

PBRM1 directs PBAF to pericentromeres and protects centromere integrity

Karen A. Lane, Najaf Amin, Jessica A. Downs, Frank T. Zenke, Jyoti S. Choudhary, Shane Foo, Alison Harrod, Alan A. Melcher, Federica Schiavoni, Lillian Wu, Hugang Feng, Theodoros I. Roumeliotis, Katheryn Begg
article en
8 citations

Abstract

The specialised structure of the centromere is critical for effective chromosome segregation, but its repetitive nature makes it vulnerable to rearrangements. Centromere fragility can drive tumorigenesis, but protective mechanisms preventing fragility are still not fully understood. The PBAF chromatin remodelling complex is frequently misregulated in cancer, but its role in cancer is incompletely characterized. Here, we identify PBAF as a protector of centromere and pericentromere structure with profound consequences for genome stability. A conserved feature of isogenic cell lines lacking PBRM1, a subunit of PBAF, is compromised centromere and pericentromere integrity. PBAF is present at these regions, and binding patterns of PBAF and H3K9 methylation change when PBRM1 is absent. PBRM1 loss creates a dependence on the spindle assembly checkpoint, which represents a therapeutic vulnerability. Importantly, we find that even in the absence of any perturbations, PBRM1 loss leads to centromere fragility, thus identifying a key player in centromere protection.

Nature CommunicationsVol. 16(1)
Institute of Cancer Research (GB), Merck KGaA, Darmstadt (Germany) (DE), The Francis Crick Institute (GB), Cancer Research UK (GB), London Cancer (GB), Institute of Cancer Research (CA)
Cancer Research UK, Medical Research Council
Openalex Percentile: Top 1%
Chromosomal and Genetic Variations
14.00
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.