Ectopic centromere nucleation by CENP--a in fission yeast

Area of Science:

• Cell Biology
• Genetics
• Epigenetics

Background:

• The centromere is crucial for accurate chromosome segregation, with its function epigenetically specified.
• Centromere protein-A (CENP-A) is essential for centromere identity and kinetochore assembly.
• Mechanisms preventing ectopic centromere formation (neocentromeres) are not well understood.

Purpose of the Study:

• To investigate the consequences of CENP-A overexpression in fission yeast.
• To understand the mechanisms protecting against ectopic CENP-A assembly.

Main Methods:

• Overexpression of CENP-A(Cnp1) in fission yeast.
• Analysis of chromosome segregation and kinetochore component recruitment.
• Investigating the role of histone H3/H4 and CENP-A's N-terminal domain.

Main Results:

• Ectopic CENP-A assembly occurred at noncentromeric chromatin, particularly near heterochromatin.
• Overexpression led to severe chromosome missegregation and spindle disorganization.
• Ectopic CENP-A chromatin persisted across cell divisions and was suppressed by H3/H4 co-overexpression.

Conclusions:

• The N-terminal domain of CENP-A is critical for preventing its ectopic assembly.
• Ectopic CENP-A assembly is regulated by ubiquitin-dependent proteolysis.
• These findings shed light on the protection mechanisms against neocentromere formation.