RRC ID 65718
Author Schmücker A, Lei B, Lorković ZJ, Capella M, Braun S, Bourguet P, Mathieu O, Mechtler K, Berger F.
Title Crosstalk between H2A variant-specific modifications impacts vital cell functions.
Journal PLoS Genet
Abstract Selection of C-terminal motifs participated in evolution of distinct histone H2A variants. Hybrid types of variants combining motifs from distinct H2A classes are extremely rare. This suggests that the proximity between the motif cases interferes with their function. We studied this question in flowering plants that evolved sporadically a hybrid H2A variant combining the SQ motif of H2A.X that participates in the DNA damage response with the KSPK motif of H2A.W that stabilizes heterochromatin. Our inventory of PTMs of H2A.W variants showed that in vivo the cell cycle-dependent kinase CDKA phosphorylates the KSPK motif of H2A.W but only in absence of an SQ motif. Phosphomimicry of KSPK prevented DNA damage response by the SQ motif of the hybrid H2A.W/X variant. In a synthetic yeast expressing the hybrid H2A.W/X variant, phosphorylation of KSPK prevented binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and impaired response to DNA damage. Our findings illustrate that PTMs mediate interference between the function of H2A variant specific C-terminal motifs. Such interference could explain the mutual exclusion of motifs that led to evolution of H2A variants.
Volume 17(6)
Pages e1009601
Published 2021-6-1
DOI 10.1371/journal.pgen.1009601
PMID 34086674
PMC PMC8208582
MeSH Amino Acid Sequence Arabidopsis / genetics* Arabidopsis / metabolism Arabidopsis Proteins / genetics* Arabidopsis Proteins / metabolism Cell Culture Techniques Cell Cycle / genetics Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism Cyclin-Dependent Kinases / genetics Cyclin-Dependent Kinases / metabolism DNA Damage Evolution, Molecular Gene Expression Regulation, Plant* Heterochromatin / chemistry Heterochromatin / metabolism Histones / genetics* Histones / metabolism Phosphorylation Plant Cells / metabolism Plants, Genetically Modified Protein Isoforms / genetics Protein Isoforms / metabolism Protein Processing, Post-Translational* Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism Sequence Alignment Sequence Homology, Amino Acid Transgenes
IF 5.175
Arabidopsis / Cultured plant cells, genes rpc00008