Back to Search
Start Over
Lighting Up pre-mRNA recognition
- Source :
- Molecular Cell
- Publication Year :
- 2014
-
Abstract
- Summary Maternal metabolism provides essential nutrients to enable embryonic development. However, both mother and embryo produce reactive metabolites that can damage DNA. Here we discover how the embryo is protected from these genotoxins. Pregnant mice lacking Aldh2, a key enzyme that detoxifies reactive aldehydes, cannot support the development of embryos lacking the Fanconi anemia DNA repair pathway gene Fanca. Remarkably, transferring Aldh2−/−Fanca−/− embryos into wild-type mothers suppresses developmental defects and rescues embryonic lethality. These rescued neonates have severely depleted hematopoietic stem and progenitor cells, indicating that despite intact maternal aldehyde catabolism, fetal Aldh2 is essential for hematopoiesis. Hence, maternal and fetal aldehyde detoxification protects the developing embryo from DNA damage. Failure of this genome preservation mechanism might explain why birth defects and bone marrow failure occur in Fanconi anemia, and may have implications for fetal well-being in the many women in Southeast Asia that are genetically deficient in ALDH2.<br />Graphical Abstract<br />Highlights • Maternal aldehydes must be catabolized to prevent fetal DNA damage • Fetal DNA repair counteracts DNA damage caused by maternal aldehydes • Aldh2−/−Rev1−/− mice do not phenocopy Aldh2−/−Fanca−/− mice • Maternal and fetal endogenous aldehydes corrupt development and hematopoiesis<br />During pregnancy, both mother and embryo produce reactive metabolites that can damage DNA. Oberbeck et al. find that there are distinct spatial and temporal roles for maternal and fetal aldehyde detoxification in protecting the developing embryo from DNA damage, and thus from accumulating developmental defects.
- Subjects :
- Population
Aldehyde dehydrogenase
Acetaldehyde
Bioinformatics
Article
chemistry.chemical_compound
Fanconi anemia
Pregnancy
hemic and lymphatic diseases
medicine
Animals
Humans
Binding site
education
Molecular Biology
education.field_of_study
Ethanol
biology
Fanconi Anemia Complementation Group A Protein
Cell Biology
Aldehyde Dehydrogenase
medicine.disease
Embryo, Mammalian
Yeast
Fanconi Anemia
chemistry
Biochemistry
embryonic structures
biology.protein
Female
Precursor mRNA
Subjects
Details
- ISSN :
- 10974164
- Volume :
- 55
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular cell
- Accession number :
- edsair.doi.dedup.....7d601b8f8d319f72ded3a87c1b6612f0