GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16777961

From GONUTS
Jump to: navigation, search
Citation

Orii, KE, Lee, Y, Kondo, N and McKinnon, PJ (2006) Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. Proc. Natl. Acad. Sci. U.S.A. 103:10017-22

Abstract

The repair of DNA double-strand breaks (DSBs) occurs via nonhomologous end-joining (NHEJ) or homologous recombination (HR). These mechanistically distinct pathways are critical for maintenance of genomic integrity and organismal survival. Although inactivation of either pathway leads to embryonic lethality, here we show selective requirements for each DNA DSB repair pathway at different stages of mammalian nervous system development. DNA damage-induced apoptosis resulting from inactivation of HR (Xrcc2 deficiency) only occurred in proliferating neural precursor cells, whereas disruption of NHEJ (DNA ligase IV deficiency) mainly affected differentiating cells at later developmental stages. Therefore, these data suggest that NHEJ is dispensable for a substantial portion of early development because DSB repair during this period utilizes HR. Moreover, DNA damage-induced apoptosis required the ataxia telangiectasia mutated (Atm) kinase after disruption of NHEJ, but not HR, during neurogenesis. However, embryonic lethality arising from disruption of either repair pathway was rescued by loss of p53 and resulted in specific tumor types reflective of the particular DSB repair pathway inactivated. Thus, these data reveal distinct tissue- and cell-type requirements for each DNA DSB repair pathway during neural development and provide insights for understanding the contributions of DNA DSB responses to disease.

Links

PubMed PMC1502498 Online version:10.1073/pnas.0602436103

Keywords

Animals; Apoptosis/genetics; Brain/embryology; Cell Cycle Proteins/genetics; DNA Damage; DNA Ligases/genetics; DNA Repair/genetics; DNA-Binding Proteins/genetics; Mice; Mice, Neurologic Mutants; Nervous System/embryology; Protein-Serine-Threonine Kinases/genetics; Recombination, Genetic/genetics; Tumor Suppressor Proteins/genetics

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

See Help:References for how to manage references in GONUTS.