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A kinase‐dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion
- Source :
- EMBO reports. 19:43-56
- Publication Year :
- 2017
- Publisher :
- EMBO, 2017.
-
Abstract
- Sister‐chromatid cohesion mediated by the cohesin complex is fundamental for precise chromosome segregation in mitosis. Through binding the cohesin subunit Pds5, Wapl releases the bulk of cohesin from chromosome arms in prophase, whereas centromeric cohesin is protected from Wapl until anaphase onset. Strong centromere cohesion requires centromeric localization of the mitotic histone kinase Haspin, which is dependent on the interaction of its non‐catalytic N‐terminus with Pds5B. It remains unclear how Haspin fully blocks the Wapl–Pds5B interaction at centromeres. Here, we show that the C‐terminal kinase domain of Haspin (Haspin‐KD) binds and phosphorylates the YSR motif of Wapl (Wapl‐YSR), thereby directly inhibiting the YSR motif‐dependent interaction of Wapl with Pds5B. Cells expressing a Wapl‐binding‐deficient mutant of Haspin or treated with Haspin inhibitors show centromeric cohesion defects. Phospho‐mimetic mutation in Wapl‐YSR prevents Wapl from binding Pds5B and releasing cohesin. Forced targeting Haspin‐KD to centromeres partly bypasses the need for Haspin–Pds5B interaction in cohesion protection. Taken together, these results indicate a kinase‐dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis.
- Subjects :
- 0301 basic medicine
Cohesin complex
Chromosomal Proteins, Non-Histone
Amino Acid Motifs
Centromere
Cell Cycle Proteins
Chromatids
Protein Serine-Threonine Kinases
Prophase
Biochemistry
Chromosome segregation
03 medical and health sciences
0302 clinical medicine
Chromosome Segregation
Proto-Oncogene Proteins
Genetics
Humans
Phosphorylation
Molecular Biology
Mitosis
Anaphase
Cohesin
Chemistry
Scientific Reports
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Molecular biology
Cell biology
DNA-Binding Proteins
Establishment of sister chromatid cohesion
030104 developmental biology
Mutation
biological phenomena, cell phenomena, and immunity
Carrier Proteins
030217 neurology & neurosurgery
HeLa Cells
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 14693178 and 1469221X
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- EMBO reports
- Accession number :
- edsair.doi.dedup.....82ef71341a6d36bd6d589f5bf6a7e810