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Craig W Gambogi1,2,3,4, Nootan Pandey1,2,3, Jennine M Dawicki-McKenna1,2,3

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Mammalian centromeres use unique DNA sequences for faithful inheritance. A divergent centromere in Mus pahari utilizes abundant CENP-B to balance microtubule interactions for accurate cell division.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Epigenetics

Background:

  • Mammalian centromeres are crucial for genetic inheritance, characterized by repetitive DNA.
  • Centromere identity is specified by centromere protein-A (CENP-A) nucleosomes.
  • Satellite DNA evolution plays a role in centromere function.

Purpose of the Study:

  • To investigate the molecular composition and function of centromeres in the mouse species Mus pahari.
  • To characterize a novel satellite repeat (π-satellite) and its role in centromere formation.
  • To understand how divergent centromeric sequences influence chromosome segregation.

Main Methods:

  • Identification and characterization of satellite DNA repeats (π-satellite and π-satB).
  • Analysis of centromere protein binding (CENP-A, CENP-B).
  • Investigation of kinetochore and inner centromere component recruitment.

Main Results:

  • Mus pahari centromeres house CENP-A at π-satellite repeats with limited CENP-B sites.
  • One chromosome exhibits a divergent centromere with extensive π-satB repeats and numerous CENP-B boxes.
  • High CENP-B abundance in the divergent centromere promotes specific kinetochore and inner centromere protein accumulation.

Conclusions:

  • The divergent centromere in Mus pahari achieves high-fidelity segregation through a unique molecular composition.
  • A balance of microtubule-binding proteins, influenced by CENP-B, is critical for the function of this novel centromere.
  • Centromeric DNA sequence variation can lead to distinct mechanisms for ensuring accurate chromosome inheritance.