title: NatB domain-containing CRA-1 antagonizes hydrolase ACER-1 linking acetyl-CoA metabolism to the initiation of recombination during C. elegans meiosis.
abstract: The formation of DNA double-strand breaks (DSBs) must take place during meiosis to ensure the formation of crossovers, which are required for accurate chromosome segregation, therefore avoiding aneuploidy. However, DSB formation must be tightly regulated to maintain genomic integrity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. We show here that global histone acetylation levels undergo changes throughout meiotic progression. Moreover, perturbations to global histone acetylation levels are accompanied by changes in the frequency of DSB formation in C. elegans. We provide evidence that the regulation of histone acetylation requires CRA-1, a NatB domain-containing protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A (acetyl-CoA) by antagonizing ACER-1, a previously unknown and conserved acetyl-CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook containing protein. We propose that this newly defined protein network links acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone acetylation.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Hyun-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Elia
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Monica P
authors.initials: MP
authors.lastname: Colaiácovo
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000104:Acetyl-CoA Hydrolase / Q000378:metabolism*; D000107:Acetylation; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D006657:Histones / Q000378:metabolism; D011995:Recombination, Genetic; D014960:X Chromosome / Q000378:metabolism
chemical_list: C530202:CRA-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D006657:Histones; D000105:Acetyl Coenzyme A; C000603421:ACER-1 protein, C elegans; D000104:Acetyl-CoA Hydrolase