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

PLoS One

Program in Molecular & Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA, United States of America.

Published: April 2024

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11045136PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0300732PLOS

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