Osaka, Japan – In a groundbreaking study published in The EMBO Journal, researchers from The University of Osaka have uncovered a previously unknown pathway crucial to the process of cell division. Despite the vast amount of genetic material in human cells—approximately three billion base pairs—this material must be accurately divided and allocated during cell division. The centromere, a key chromosomal region, plays a critical role in this process, yet the exact mechanisms have remained elusive until now.
The study reveals an additional pathway by which the DNA-packaging histone CENP-A associates with the centromere, facilitated by the Holliday Junction Recognition Protein (HJURP). This discovery is significant for understanding how chromosomes are structured and genes expressed correctly, ensuring successful cell division.
Unveiling the Role of HJURP and CENP-C
The research centered on HJURP, a chaperone protein that guides centromere-identifying components to their correct chromosomal sites. The study found that eliminating the expression of two cell components, CENP-C and Mis18C, disrupted HJURP localization at the centromere. This double knockout process highlighted a parallel pathway involving CENP-C, which can substitute for Mis18C’s role in facilitating CENP-A deposition.
“Although it was known that Mis18C recognizes the chaperone HJURP to enable CENP-A’s deposition onto centromeres, we found that CENP-C can actually occupy Mis18C’s role in this process, providing a parallel pathway that helps ensure successful and timely mitosis or meiosis,” said senior author Tatsuo Fukagawa.
The team further identified specific residues of HJURP that enable its binding to CENP-C, a discovery that could pave the way for new research into centromere function.
Implications for Cell Division and Beyond
Building on these findings, the researchers conducted analyses in DT40 chicken cells, confirming the essential nature of these interactions for centromere function during cell division. The absence of interaction between HJURP and CENP-C resulted in mitotic errors and slowed cell growth. Moreover, the removal of Mis18C prevented CENP-A incorporation into chromatin, leaving cellular machinery unable to locate the centromere.
“Our work reveals that this sequence-independent epigenetic mechanism of centromere specification has greater diversity than previously thought,” explained lead author Tetsuya Hori. “Given how biologically fundamental the processes of mitosis and meiosis are, our finding that the cell has independent pathways for flagging the location of each chromosome’s centromere is valuable.”
The discovery of dual pathways for recruiting HJURP for CENP-A deposition provides a solid foundation for future studies on centromere mechanisms and diseases related to cell division errors.
Future Research and Broader Impact
The implications of this study extend beyond basic biology, offering potential insights into medical conditions involving faulty cell division, such as cancer. Understanding the mechanisms behind centromere function could lead to new therapeutic targets and strategies for treating such diseases.
The article, “Dual pathways via CENP-C and Mis18C recruit HJURP for CENP-A deposition into vertebrate centromeres,” is available in The EMBO Journal and can be accessed at https://doi.org/10.1038/s44318-025-00674-z.
About The University of Osaka
Founded in 1931 as one of Japan’s seven imperial universities, The University of Osaka is a leading institution known for its comprehensive academic offerings and commitment to innovation. Recognized globally, the university plays a pivotal role in advancing scientific research and technology, contributing to societal development and transformation.
For more information, visit The University of Osaka’s website.
