Sexual reproduction culminates in a totipotent zygote with the potential to produce a whole organism. Sperm chromatin reorganization and epigenetic reprogramming that alter DNA and histone modifications generate a totipotent embryo. Active DNA demethylation of the paternal genome has been proposed to involve base excision and DNA repair-based mechanisms. The nature and consequence of DNA lesions generated during reprogramming are not known. Using mouse genetics and chemical biology, we discovered that Tet3-dependent zygotic reprogramming generates paternal DNA lesions that are monitored by a surveillance mechanism. In vivo structure-function rescue assays revealed that cohesin-dependent repair of paternal DNA lesions prevents activation of a Chk1-dependent checkpoint that delays mitotic entry. Culturing conditions affect checkpoint stringency, which has implications for human in vitro fertilization. We propose the zygotic checkpoint senses DNA lesions generated during paternal DNA demethylation and ensures reprogrammed loci are repaired before mitosis to prevent chromosome fragmentation, embryo loss, and infertility.
Pubmed ID: 27916276 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsA division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsLaser capture microdissection system that includes infrared lasers. It can be used for laser capture microdissection LCM, ultraviolet UV laser cutting, sanger sequencing, next generation sequencing, and quantitative PCR.
View all literature mentionsThis polyclonal targets 5-Hydroxymethylcytosine (5-hmC)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets gamma H2A.X (phospho S139)
View all literature mentionsThis polyclonal targets Human XRCC1
View all literature mentionsThis monoclonal targets BrdU
View all literature mentionsThis monoclonal targets Methylcytidine
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsMus musculus with name B6.FVB-Tg(Zp3-cre)3Mrt/J from IMSR.
View all literature mentionsThis polyclonal targets 5-Hydroxymethylcytosine (5-hmC)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets gamma H2A.X (phospho S139)
View all literature mentionsThis polyclonal targets Human XRCC1
View all literature mentionsThis monoclonal targets BrdU
View all literature mentionsThis monoclonal targets Methylcytidine
View all literature mentionsMus musculus with name B6.FVB-Tg(Zp3-cre)3Mrt/J from IMSR.
View all literature mentionsThis monoclonal targets gamma H2A.X (phospho S139)
View all literature mentionsThis polyclonal targets Human XRCC1
View all literature mentionsThis monoclonal targets BrdU
View all literature mentionsThis monoclonal targets Methylcytidine
View all literature mentions