Scholarlink

<p>The chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B kinase) ensures accurate chromosome segregation by orchestrating sister chromatid cohesion, error correction of kinetochore-microtubule attachments, and spindle assembly checkpoint signaling. Correct spatiotemporal regulation of CPC is critical for its function. Phosphorylations of histone H3 Thr3 and histone H2A Thr120 and modification-independent nucleosome interactions involving Survivin and Borealin contribute to CPC centromere enrichment. However, how various nucleosome binding elements collectively contribute to CPC centromere enrichment at the mechanistic level, and whether CPC has any non-catalytic role at centromere remain open questions. Combining the high-resolution cryo-EM structure of a CPC-bound H3Thr3ph nucleosome with atomic force microscopy and biochemical and cellular assays, we demonstrate that CPC employs multipartite interactions, which facilitate its engagement with nucleosome acidic patch and the DNA entry-exit site. Perturbing the CPC-nucleosome interaction compromises chromatin protection against MNase digestion in vitro, and centromeric chromatin stability and error-free chromosome segregation in cells. Our work suggests a non-catalytic chromatin-stabilizing role of CPC in maintaining centromeric chromatin features critical for kinetochore function.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月27日

查看全文
  • Anjitha Gireesh,
  • Maria Alba Abad,
  • Ryu-Suke Nozawa,
  • Paula Sotelo-Parrilla,
  • Léa C Dury,
  • Mariia Likhodeeva,
  • Martin Wear,
  • Christos Spanos,
  • Cristina Cardenal Peralta,
  • Juri Rappsilber,
  • Karl-Peter Hopfner,
  • Marcus D Wilson,
  • Willem Vanderlinden,
  • Toru Hirota,
  • A Arockia Jeyaprakash

摘要

The chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B kinase) ensures accurate chromosome segregation by orchestrating sister chromatid cohesion, error correction of kinetochore-microtubule attachments, and spindle assembly checkpoint signaling. Correct spatiotemporal regulation of CPC is critical for its function. Phosphorylations of histone H3 Thr3 and histone H2A Thr120 and modification-independent nucleosome interactions involving Survivin and Borealin contribute to CPC centromere enrichment. However, how various nucleosome binding elements collectively contribute to CPC centromere enrichment at the mechanistic level, and whether CPC has any non-catalytic role at centromere remain open questions. Combining the high-resolution cryo-EM structure of a CPC-bound H3Thr3ph nucleosome with atomic force microscopy and biochemical and cellular assays, we demonstrate that CPC employs multipartite interactions, which facilitate its engagement with nucleosome acidic patch and the DNA entry-exit site. Perturbing the CPC-nucleosome interaction compromises chromatin protection against MNase digestion in vitro, and centromeric chromatin stability and error-free chromosome segregation in cells. Our work suggests a non-catalytic chromatin-stabilizing role of CPC in maintaining centromeric chromatin features critical for kinetochore function.