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Centromere Innovations Within a Mouse Species.

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

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The mouse species Mus pahari exhibits unique centromere structures, with one chromosome featuring a large, homogenized repeat (π-satB) that recruits abundant CENP-B. This novel centromere composition ensures faithful chromosome segregation during cell division.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Epigenetics

Background:

  • Mammalian centromeres are crucial for faithful chromosome segregation during cell division.
  • Centromeres are typically composed of repetitive DNA sequences that evolve rapidly.
  • The centromere-specific histone H3 variant, CENP-A, nucleates centromere identity.

Approach:

  • Investigated the centromeric DNA and protein composition in the mouse species Mus pahari.
  • Identified a novel satellite repeat, termed π-satellite (π-sat), and its variant π-satB.
  • Utilized molecular and cytological methods to analyze CENP-A and CENP-B localization and kinetochore assembly.

Key Points:

  • Mus pahari centromeres house CENP-A at the nexus of π-satellite repeats, with limited CENP-B recruitment sites.
  • A distinct chromosome in M. pahari possesses a large, homogenized π-satB repeat array with over 20,000 CENP-B boxes.
  • High CENP-B abundance at the π-satB centromere influences kinetochore composition, including microtubule-binding proteins and a kinesin.

Conclusions:

  • The unique centromere structure in Mus pahari, particularly the π-satB variant, demonstrates an alternative mechanism for centromere formation and function.
  • The differential molecular composition of centromeres within the same genome allows for stable coexistence and high-fidelity segregation.
  • This study provides insights into the evolutionary plasticity of centromeres and their role in genetic inheritance.