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Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila

Many metabolic enzymes are evolutionarily highly conserved and serve a central function in the catabolism and anabolism of cells. The serine hydroxymethyl transferase (SHMT) catalyzing the conversion of serine and glycine and vice versa feeds into tetrahydrofolate (THF)-mediated C1 metabolism. We id...

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Autores principales: Winkler, Franziska, Kriebel, Maria, Clever, Michaela, Gröning, Stephanie, Großhans, Jörg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499137/
https://www.ncbi.nlm.nih.gov/pubmed/28515048
http://dx.doi.org/10.1534/g3.117.043133
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author Winkler, Franziska
Kriebel, Maria
Clever, Michaela
Gröning, Stephanie
Großhans, Jörg
author_facet Winkler, Franziska
Kriebel, Maria
Clever, Michaela
Gröning, Stephanie
Großhans, Jörg
author_sort Winkler, Franziska
collection PubMed
description Many metabolic enzymes are evolutionarily highly conserved and serve a central function in the catabolism and anabolism of cells. The serine hydroxymethyl transferase (SHMT) catalyzing the conversion of serine and glycine and vice versa feeds into tetrahydrofolate (THF)-mediated C1 metabolism. We identified a Drosophila mutation in SHMT (CG3011) in a screen for blastoderm mutants. Embryos from SHMT mutant germline clones specifically arrest the cell cycle in interphase 13 at the time of the midblastula transition (MBT) and prior to cellularization. The phenotype is due to a loss of enzymatic activity as it cannot be rescued by an allele with a point mutation in the catalytic center but by an allele based on the SHMT coding sequence from Escherichia coli. The onset of zygotic gene expression and degradation of maternal RNAs in SHMT mutant embryos are largely similar to that in wild-type embryos. The specific timing of the defects in SHMT mutants indicates that at least one of the SHMT-dependent metabolites becomes limiting in interphase 13, if it is not produced by the embryo. Our data suggest that mutant eggs contain maternally-provided and SHMT-dependent metabolites in amounts that suffice for early development until interphase 13.
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spelling pubmed-54991372017-07-07 Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila Winkler, Franziska Kriebel, Maria Clever, Michaela Gröning, Stephanie Großhans, Jörg G3 (Bethesda) Investigations Many metabolic enzymes are evolutionarily highly conserved and serve a central function in the catabolism and anabolism of cells. The serine hydroxymethyl transferase (SHMT) catalyzing the conversion of serine and glycine and vice versa feeds into tetrahydrofolate (THF)-mediated C1 metabolism. We identified a Drosophila mutation in SHMT (CG3011) in a screen for blastoderm mutants. Embryos from SHMT mutant germline clones specifically arrest the cell cycle in interphase 13 at the time of the midblastula transition (MBT) and prior to cellularization. The phenotype is due to a loss of enzymatic activity as it cannot be rescued by an allele with a point mutation in the catalytic center but by an allele based on the SHMT coding sequence from Escherichia coli. The onset of zygotic gene expression and degradation of maternal RNAs in SHMT mutant embryos are largely similar to that in wild-type embryos. The specific timing of the defects in SHMT mutants indicates that at least one of the SHMT-dependent metabolites becomes limiting in interphase 13, if it is not produced by the embryo. Our data suggest that mutant eggs contain maternally-provided and SHMT-dependent metabolites in amounts that suffice for early development until interphase 13. Genetics Society of America 2017-05-17 /pmc/articles/PMC5499137/ /pubmed/28515048 http://dx.doi.org/10.1534/g3.117.043133 Text en Copyright © 2017 Winkler et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Winkler, Franziska
Kriebel, Maria
Clever, Michaela
Gröning, Stephanie
Großhans, Jörg
Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila
title Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila
title_full Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila
title_fullStr Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila
title_full_unstemmed Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila
title_short Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila
title_sort essential function of the serine hydroxymethyl transferase (shmt) gene during rapid syncytial cell cycles in drosophila
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499137/
https://www.ncbi.nlm.nih.gov/pubmed/28515048
http://dx.doi.org/10.1534/g3.117.043133
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