Chromodomain mutation in S. pombe Kat5/Mst1 affects centromere dynamics and DNA repair

KAT5 (S. pombe Mst1, human TIP60) is a MYST family histone acetyltransferase conserved from yeast to humans that is involved in multiple cellular activities. This family is characterized in part by containing a chromodomain, a motif associated with binding methylated histones. We show that a chromod...

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Bibliographic Details
Published in:PloS one 2024-04, Vol.19 (4), p.e0300732
Main Authors: Li, Tingting, Petreaca, Ruben C, Forsburg, Susan L
Format: Article
Language:English
Subjects:
Analysis
Biology and Life Sciences
Camptothecin - pharmacology
Centromere - genetics
Centromere - metabolism
Chromosomes
DNA
DNA binding proteins
DNA Damage
DNA Repair
Gene mutations
Genetic aspects
Health aspects
Heterochromatin - genetics
Heterochromatin - metabolism
Histone Acetyltransferases - genetics
Histone Acetyltransferases - metabolism
Histones
Humans
Lysine Acetyltransferase 5 - genetics
Lysine Acetyltransferase 5 - metabolism
Methylation
Mutation
Physical Sciences
Research and Analysis Methods
Schizosaccharomyces - drug effects
Schizosaccharomyces - genetics
Schizosaccharomyces - metabolism
Schizosaccharomyces pombe Proteins - genetics
Schizosaccharomyces pombe Proteins - metabolism
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Summary:KAT5 (S. pombe Mst1, human TIP60) is a MYST family histone acetyltransferase conserved from yeast to humans that is involved in multiple cellular activities. This family is characterized in part by containing a chromodomain, a motif associated with binding methylated histones. We show that a chromodomain mutation in the S. pombe Kat5, mst1-W66R, has defects in pericentromere silencing. mst1-W66R is sensitive to camptothecin (CPT) but only at an increased temperature of 36°C, although it is proficient for growth at this temperature. We also describe a de-silencing effect at the pericentromere by CPT that is independent of RNAi and methylation machinery. We also show that mst1-W66R disrupts recruitment of proteins to repair foci in response to camptothecin-induced DNA damage. Our data suggest a function of Mst1 chromodomain in centromere heterochromatin formation and a separate role in genome-wide damage repair in CPT.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0300732