NatB Domain-Containing CRA-1 Antagonizes Hydrolase ACER-1 Linking Acetyl-CoA Metabolism to the Initiation of Recombination during . Meiosis
Achieving accurate chromosome segregation is a critical outcome for any cell division process. Programmed DNA double-strand break formation is a central mechanism set in place to promote faithful chromosome segregation during meiosis. A subset of these DSBs is repaired as crossovers via reciprocal exchange of genetic information between homologous chromosomes resulting in physical attachments (chiasmata) between homologs, which ensure proper chromosome alignment at the metaphase plate at meiosis I, and also promote genetic diversity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. In this study, we found that CRA-1, a NatB domain-containing protein, promotes histone acetylation by maintaining the levels of acetyl-Coenzyme A (acetyl-CoA) through 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 leveraged this discovery to find a connection between the levels of acetyl-CoA, histone acetylation and DSB formation. We identified a novel protein network that links the regulation of DSB formation to the modulation of global levels of histone acetylation, and revealed a link between metabolism and the regulation of DSB formation.
Vyšlo v časopise:
NatB Domain-Containing CRA-1 Antagonizes Hydrolase ACER-1 Linking Acetyl-CoA Metabolism to the Initiation of Recombination during . Meiosis. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005029
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005029
Souhrn
Achieving accurate chromosome segregation is a critical outcome for any cell division process. Programmed DNA double-strand break formation is a central mechanism set in place to promote faithful chromosome segregation during meiosis. A subset of these DSBs is repaired as crossovers via reciprocal exchange of genetic information between homologous chromosomes resulting in physical attachments (chiasmata) between homologs, which ensure proper chromosome alignment at the metaphase plate at meiosis I, and also promote genetic diversity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. In this study, we found that CRA-1, a NatB domain-containing protein, promotes histone acetylation by maintaining the levels of acetyl-Coenzyme A (acetyl-CoA) through 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 leveraged this discovery to find a connection between the levels of acetyl-CoA, histone acetylation and DSB formation. We identified a novel protein network that links the regulation of DSB formation to the modulation of global levels of histone acetylation, and revealed a link between metabolism and the regulation of DSB formation.
Zdroje
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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