Phosphorylation of Drosophila CENP-A on serine 20 regulates protein turn-over and centromere-specific loading.
Amino Acid Sequence
Animals
Casein Kinase II
/ metabolism
Centromere
/ metabolism
Centromere Protein A
/ chemistry
Chromatin
/ metabolism
Drosophila Proteins
/ chemistry
Drosophila melanogaster
/ metabolism
Mutant Proteins
/ metabolism
Phosphorylation
Phosphoserine
/ metabolism
Protein Binding
Proteolysis
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 11 2019
18 11 2019
Historique:
accepted:
11
09
2019
revised:
06
09
2019
received:
14
05
2019
pubmed:
20
9
2019
medline:
19
5
2020
entrez:
20
9
2019
Statut:
ppublish
Résumé
Centromeres are specialized chromosomal regions epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A is required for kinetochore formation which is essential for chromosome segregation during mitosis. Spatial restriction of CENP-A to the centromere is tightly controlled. Its overexpression results in ectopic incorporation and the formation of potentially deleterious neocentromeres in yeast, flies and in various human cancers. While the contribution of posttranslational modifications of CENP-A to these processes has been studied in yeast and mammals to some extent, very little is known about Drosophila melanogaster. Here, we show that CENP-A is phosphorylated at serine 20 (S20) by casein kinase II and that in mitotic cells, the phosphorylated form is enriched on chromatin. Importantly, our results reveal that S20 phosphorylation regulates the turn-over of prenucleosomal CENP-A by the SCFPpa-proteasome pathway and that phosphorylation promotes removal of CENP-A from ectopic but not from centromeric sites in chromatin. We provide multiple lines of evidence for a crucial role of S20 phosphorylation in controlling restricted incorporation of CENP-A into centromeric chromatin in flies. Modulation of the phosphorylation state of S20 may provide the cells with a means to fine-tune CENP-A levels in order to prevent deleterious loading to extra-centromeric sites.
Identifiants
pubmed: 31535131
pii: 5571580
doi: 10.1093/nar/gkz809
pmc: PMC6847487
doi:
Substances chimiques
Centromere Protein A
0
Chromatin
0
Cid protein, Drosophila
0
Drosophila Proteins
0
Mutant Proteins
0
Phosphoserine
17885-08-4
Casein Kinase II
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10754-10770Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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