Vinutha Balachandra, Roshan L Shrestha, Colin M Hammond, Shinjen Lin, Ivo A Hendriks, Subhash Chandra Sethi, Lu Chen, Samantha Sevilla, Natasha J Caplen, Raj Chari, Tatiana S Karpova, Katherine McKinnon, Matthew Am Todd, Vishal Koparde, Ken Chih-Chien Cheng, Michael L Nielsen, Anja Groth, Munira A Basrai
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...
April 10, 2024: EMBO Journal