Centromere Specification Pathways Identified
Genetic material, comprising approximately three billion base pairs in humans, necessitates accurate and equal division during cell replication. The centromere, located on each chromosome, serves as the attachment site for cellular machinery facilitating chromosome division; however, the precise mechanisms involved have not been fully understood.
New Pathway Discovery
Researchers at The University of Osaka have identified an additional pathway that governs how the DNA-packaging histone CENP-A associates with and specifies the centromere's location. This process is essential for maintaining chromosome structure and appropriate gene expression.
Role of Chaperone Proteins
The study focused on the Holliday Junction Recognition Protein (HJURP), a chaperone protein responsible for guiding centromere-identifying cell components to correct chromosomal sites. It was observed that HJURP did not localize at the centromere when the expression of both CENP-C and Mis18C cell components was eliminated through a double knockout process.
While Mis18C was previously known to recognize HJURP, enabling CENP-A's deposition onto centromeres, the study revealed that CENP-C can assume Mis18C's role in this process. This suggests a parallel pathway that supports successful and timely mitosis or meiosis. Researchers also identified specific residues within HJURP that facilitate its binding to CENP-C.
Experimental Validation and Implications
Further analyses in DT40 chicken cells confirmed that these interactions are crucial for centromere function during cell division. When HJURP and CENP-C failed to interact, errors in mitosis occurred, leading to slowed cell growth. A combined absence of this interaction and the removal of Mis18C prevented CENP-A from incorporating into chromatin, thereby inhibiting cellular machinery from identifying the centromere's location.
These findings indicate that the sequence-independent epigenetic mechanism of centromere specification exhibits greater diversity than previously understood. The existence of dual pathways for recruiting HJURP for CENP-A deposition provides a foundation for future research into centromere mechanisms and diseases associated with cell division errors.