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Transcription destabilizes centromere function.

Yu Nakabayashi1, Masayuki Seki1

  • 1Division of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan.

Biochemical and Biophysical Research Communications
|November 29, 2021
PubMed
Summary
This summary is machine-generated.

Transcription through the centromere disrupts microtubule-kinetochore attachments, leading to chromosome mis-segregation. This occurs because centromeric transcription displaces essential centromere proteins, impacting mitosis fidelity.

Keywords:
CENP-ACENP-CChromosome segregationH2A.ZHistoneTranscription

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Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Faithful chromosome segregation during mitosis requires bi-oriented attachment of microtubules to the centromere.
  • Budding yeast centromeres interact with specific proteins (Cbf1, Cse4, Ndc10) and contain cis-elements (CDE-I, -II, -III).
  • Previous studies identified histone binding sites (TBS-I, -II, -III) crucial for chromosome segregation.

Purpose of the Study:

  • To elucidate the mechanism by which TBS-III deficiency leads to defective chromosome segregation.
  • To investigate the impact of centromeric transcription on centromere protein binding and chromosome segregation.

Main Methods:

  • Analysis of TBS-III deficient cells and wild-type cells with ectopic centromeric transcription.
  • Assessment of chromatin binding at the centromere and centromere protein levels.
  • Monitoring of centromeric transcription during M-phase.

Main Results:

  • Cells lacking TBS-III exhibit reduced centromere chromatin binding and lower levels of some centromere proteins.
  • Transcription through the centromere is increased during M-phase in TBS-III deficient cells.
  • Ectopic centromeric transcription in wild-type cells reduces the binding of key centromere proteins (Cse4, Mif2, Cbf1, Ndc10, Scm3).

Conclusions:

  • Centromeric transcription displaces essential centromere proteins, destabilizing centromere-microtubule interactions.
  • This displacement leads to defective chromosome segregation.
  • Histone binding residues in TBS-III play a critical role in nucleosome function during chromosome segregation.