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Distinct features of ribonucleotides within genomic DNA in Aicardi-Goutières syndrome ortholog mutants of Saccharomyces cerevisiae.
Kundnani, Deepali L; Yang, Taehwan; Gombolay, Alli L; Mukherjee, Kuntal; Newnam, Gary; Meers, Chance; Verma, Ishika; Chhatlani, Kirti; Mehta, Zeel H; Mouawad, Celine; Storici, Francesca.
Afiliación
  • Kundnani DL; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Yang T; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Gombolay AL; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Mukherjee K; Bacterial Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Newnam G; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Meers C; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Verma I; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Chhatlani K; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
  • Mehta ZH; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Mouawad C; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Storici F; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
iScience ; 27(6): 110012, 2024 Jun 21.
Article en En | MEDLINE | ID: mdl-38868188
ABSTRACT
Ribonucleoside monophosphates (rNMPs) are abundantly found within genomic DNA of cells. The embedded rNMPs alter DNA properties and impact genome stability. Mutations in ribonuclease (RNase) H2, a key enzyme for rNMP removal, are associated with the Aicardi-Goutières syndrome (AGS), a severe neurological disorder. Here, we engineered orthologs of the human RNASEH2A-G37S and RNASEH2C-R69W AGS mutations in yeast Saccharomyces cerevisiae rnh201-G42S and rnh203-K46W. Using the ribose-seq technique and the Ribose-Map bioinformatics toolkit, we unveiled rNMP abundance, composition, hotspots, and sequence context in these AGS-ortholog mutants. We found a high rNMP presence in the nuclear genome of rnh201-G42S-mutant cells, and an elevated rCMP content in both mutants, reflecting preferential cleavage of RNase H2 at rGMP. We discovered unique rNMP patterns in each mutant, showing differential activity of the AGS mutants on the leading or lagging replication strands. This study guides future research on rNMP characteristics in human genomes with AGS mutations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos