Defects in methylation of arginine 37 on CENP-A/Cse4 are compensated by the ubiquitin ligase complex Ubr2/Mub1.
The kinetochore, a supramolecular protein complex, provides the physical connection between chromatin and the microtubule and ensures correct chromosome segregation during mitosis. Centromeric regions are marked by the presence of the histone H3 variant CENP-A. Cse4, the CENP-A homologue from Saccharomyces cerevisiae, is methylated on arginine 37 in its N-terminus (R37), and the absence of methylation (cse4-R37A) causes synthetic genetic defects in combination with mutations or deletions in genes encoding components of the Ctf19/CCAN complex and with the CDEI binding protein Cbf1. Here, we report that the absence of the E3 ubiquitin ligase Ubr2 as well as its adaptor protein Mub1 suppresses the defects caused by the absence of Cse4-R37 methylation. Ubr2 is known to regulate the levels of the MIND complex component Dsn1 via ubiquitination and proteasome-mediated degradation. Accordingly, we found that overexpression of DSN1 also led to suppression of Cse4 methylation defects. Altogether, our data indicate that the absence of R37 methylation reduces the recruitment of kinetochore proteins to centromeric chromatin, and that this can be compensated for by stabilising the outer kinetochore protein Dsn1.
Anke
A
Samel
Thi Kim Loan
TKL
Nguyen
Ann E
AE
Ehrenhofer-Murray
D002352:Carrier Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D008745:Methylation; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
C092746:CSE4 protein, S cerevisiae; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C470829:Dsn1 protein, S cerevisiae; C526592:Mub1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases; C496536:Ubr2 protein, S cerevisiae
CENP-A; Psh1; arginine methylation; centromere; kinetochore; ubiquitination