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GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability.
Dokshin, Gregoriy A; Davis, Gregory M; Sawle, Ashley D; Eldridge, Matthew D; Nicholls, Peter K; Gourley, Taylin E; Romer, Katherine A; Molesworth, Luke W; Tatnell, Hannah R; Ozturk, Ahmet R; de Rooij, Dirk G; Hannon, Gregory J; Page, David C; Mello, Craig C; Carmell, Michelle A.
Afiliación
  • Dokshin GA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Davis GM; School of Health and Life Sciences, Federation University, VIC 3841, Australia.
  • Sawle AD; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Eldridge MD; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Nicholls PK; Whitehead Institute, 455 Main Street, Cambridge, MA 02142, USA.
  • Gourley TE; School of Health and Life Sciences, Federation University, VIC 3841, Australia.
  • Romer KA; Whitehead Institute, 455 Main Street, Cambridge, MA 02142, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Molesworth LW; School of Health and Life Sciences, Federation University, VIC 3841, Australia.
  • Tatnell HR; School of Health and Life Sciences, Federation University, VIC 3841, Australia.
  • Ozturk AR; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • de Rooij DG; Whitehead Institute, 455 Main Street, Cambridge, MA 02142, USA; Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584, the Netherlands; Center for Reproductive Medicine, Academic Medical Center, University of Amster
  • Hannon GJ; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
  • Page DC; Whitehead Institute, 455 Main Street, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142, USA.
  • Mello CC; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: craig.mello@umassmed.edu.
  • Carmell MA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Whitehead Institute, 455 Main Street, Cambridge, MA 02142, USA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: mcarmell@wellesley.edu.
Dev Cell ; 52(1): 53-68.e6, 2020 01 06.
Article en En | MEDLINE | ID: mdl-31839538
ABSTRACT
GCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan (DVC-1) and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. Here, we show that GCNA mutants in mouse and C. elegans display defects in genome maintenance including DNA damage, aberrant chromosome condensation, and crossover defects in mouse spermatocytes and spontaneous genomic rearrangements in C. elegans. We show that GCNA and topoisomerase II (TOP2) physically interact in both mice and worms and colocalize on condensed chromosomes during mitosis in C. elegans embryos. Moreover, C. elegans gcna-1 mutants are hypersensitive to TOP2 poison. Together, our findings support a model in which GCNA provides genome maintenance functions in the germline and may do so, in part, by promoting the resolution of TOP2 DPCs.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Espermatocitos / Proteínas Nucleares / ADN-Topoisomerasas de Tipo II / Inestabilidad Genómica / Proteínas de Unión al ADN / Replicación del ADN / Mitosis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Espermatocitos / Proteínas Nucleares / ADN-Topoisomerasas de Tipo II / Inestabilidad Genómica / Proteínas de Unión al ADN / Replicación del ADN / Mitosis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos