A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis

Murine development demands that pluripotent epiblast stem cells in the peri-implantation embryo increase from approximately 120 to 14,000 cells between embryonic days (E) 4.5 and E7.5. This is possible because epiblast stem cells can complete cell cycles in under 3 h in vivo. To ensure conceptus fit...

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Main Authors: Georgia R. Kafer, Anthony J. Cesare
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcell.2020.00416/full
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author Georgia R. Kafer
Anthony J. Cesare
author_facet Georgia R. Kafer
Anthony J. Cesare
author_sort Georgia R. Kafer
collection DOAJ
description Murine development demands that pluripotent epiblast stem cells in the peri-implantation embryo increase from approximately 120 to 14,000 cells between embryonic days (E) 4.5 and E7.5. This is possible because epiblast stem cells can complete cell cycles in under 3 h in vivo. To ensure conceptus fitness, epiblast cells must undertake this proliferative feat while maintaining genome integrity. How epiblast cells maintain genome health under such an immense proliferation demand remains unclear. To illuminate the contribution of genome stability pathways to early mammalian development we systematically reviewed knockout mouse data from 347 DDR and repair associated genes. Cumulatively, the data indicate that while many DNA repair functions are dispensable in embryogenesis, genes encoding replication stress response and homology directed repair factors are essential specifically during the peri-implantation stage of early development. We discuss the significance of these findings in the context of the unique proliferative demands placed on pluripotent epiblast stem cells.
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spelling doaj.art-35c0a25b950f441c971e3247460d15552022-12-21T19:14:59ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-05-01810.3389/fcell.2020.00416533725A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation EmbryogenesisGeorgia R. KaferAnthony J. CesareMurine development demands that pluripotent epiblast stem cells in the peri-implantation embryo increase from approximately 120 to 14,000 cells between embryonic days (E) 4.5 and E7.5. This is possible because epiblast stem cells can complete cell cycles in under 3 h in vivo. To ensure conceptus fitness, epiblast cells must undertake this proliferative feat while maintaining genome integrity. How epiblast cells maintain genome health under such an immense proliferation demand remains unclear. To illuminate the contribution of genome stability pathways to early mammalian development we systematically reviewed knockout mouse data from 347 DDR and repair associated genes. Cumulatively, the data indicate that while many DNA repair functions are dispensable in embryogenesis, genes encoding replication stress response and homology directed repair factors are essential specifically during the peri-implantation stage of early development. We discuss the significance of these findings in the context of the unique proliferative demands placed on pluripotent epiblast stem cells.https://www.frontiersin.org/article/10.3389/fcell.2020.00416/fullearly developmentembryologypluripotencyDNA damage responseDNA repairDNA replication
spellingShingle Georgia R. Kafer
Anthony J. Cesare
A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis
Frontiers in Cell and Developmental Biology
early development
embryology
pluripotency
DNA damage response
DNA repair
DNA replication
title A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis
title_full A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis
title_fullStr A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis
title_full_unstemmed A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis
title_short A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis
title_sort survey of essential genome stability genes reveals that replication stress mitigation is critical for peri implantation embryogenesis
topic early development
embryology
pluripotency
DNA damage response
DNA repair
DNA replication
url https://www.frontiersin.org/article/10.3389/fcell.2020.00416/full
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