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Characterization of novel genetic interactions between the Ipl1 Aurora kinase, the Set1 methyltransferase, and the Rad6‐Bre1 E2–E3 ubiquitin ligases
Author(s) -
Latham John A.,
Zhang Ke,
Riefler Gary M.,
Dent Sharon Y. R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a467
Subject(s) - aurora b kinase , histone h3 , biology , kinetochore , histone methyltransferase , genetics , chromosome segregation , microbiology and biotechnology , histone methylation , epigenetics , dna methylation , chromosome , gene , gene expression
Proper chromosome segregation during mitosis is crucial for the faithful inheritance of genetic material. Ipl1 is the founding member of the Aurora kinases, a fundamental class of regulators of chromosome segregation and cytokinesis from yeast to humans. In the yeast S. cerevisiae , Ipl1 phosphorylates histone H3 and several kinetochore proteins including Dam1. Another histone modifying enzyme is the methyltransferase Set1. Both the Paf1 complex and ubiquitination of H2B by Rad6/Bre1 are necessary for Set1 methylation of H3. Our lab has shown loss of SET1 suppresses the temperature sensitive (ts) and chromosome segregation defects of the ipl1‐2 mutant allele. Further experiments indicate that this suppression is through Set1 dimethylation of Dam1 at lysine 233, and that a balance of dimethylation and phosphorylation of flanking serines are important for proper Dam1 function. Here I show that Set1 is functioning within the COMPASS complex at the kinetochore. I also show that suppression of ipl1‐2 ts phenotype by loss of SET1 is not through methylation of H3 K4 as the loss of genes necessary for H3 K4 dimethylation does not suppress the ipl1‐2 ts phenotype. Surprisingly, I found that loss of RAD6, BRE1 , and the Paf1 complex member RTF1 suppress the ipl1‐2 ts phenotype, whereas loss of PAF1 does not. Therefore, some but not all of the factors required for H3 K4 dimethylation may also be required for Dam1 K233 dimethylation by Set1. This work supported by NIH T32 HD07325 & Robert A. Welch Foundation (G1371)