Phosphorylation of CENP-A on serine 7 does not control centromere function.

Area of Science:

• Epigenetics and Chromosome Biology
• Molecular Cell Biology
• Human Genetics

Background:

• Centromeres are crucial chromosomal regions for accurate cell division.
• CENP-A (centromere protein A) is a histone H3 variant that defines centromere identity.
• The role of CENP-A post-translational modifications, particularly serine 7 phosphorylation, in centromere function is debated.

Purpose of the Study:

• To investigate the necessity of CENP-A serine 7 phosphorylation for centromere assembly and function in human cells.
• To determine if CENP-A serine 7 phosphorylation is dispensable for maintaining centromere dynamics and cell viability.

Main Methods:

• Utilized gene targeting at endogenous CENP-A alleles in human cells.
• Employed gene replacement strategies to create CENP-A variants.
• Assessed CENP-C recruitment, chromosome segregation fidelity, and long-term cell viability.

Main Results:

• A CENP-A variant incapable of serine 7 phosphorylation was successfully generated.
• This modified CENP-A maintained proper CENP-C recruitment to centromeres.
• Faithful chromosome segregation and long-term cell viability were observed in cells with the non-phosphorylatable CENP-A variant.

Conclusions:

• Phosphorylation of CENP-A on serine 7 is dispensable for maintaining centromere dynamics.
• Correct centromere function, including CENP-C recruitment and chromosome segregation, can be achieved without serine 7 phosphorylation.
• This finding resolves controversy regarding the role of CENP-A serine 7 phosphorylation in centromere biology.