When parsimony backfires: neglecting DNA repair may doom neurons in Alzheimer's disease.
Taking advantage of the fact that they need not replicate their DNA, terminally differentiated neurons only repair their expressed genes and largely dispense with the burden of removing damage from most of their genome. However, they may pay a heavy price for this laxity if unforeseen circumstances, such as a pathological condition like Alzheimer's disease, cause them to re-enter the cell cycle. The lifetime accumulation of unrepaired lesions in the silent genes of neurons is likely to be significant and may result in aborting the mitotic process and triggering cell death if the cells attempt to express these dormant genes and resume DNA replication.
Nouspikel
Thierry
T
Department of Biological Sciences, Stanford University, CA 94305-5020, USA. nouspikel@stanford.edu
Hanawalt
Philip C
PC
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D016923:Cell Death; D004249:DNA Damage; D004260:DNA Repair; D015870:Gene Expression; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism* / Q000473:pathology