Developmental changes in expression and subcellular localization of the DNA repair glycosylase, MYH, in the rat brain

Mammalian cells employ a network of DNA repair pathways. DNA repair is required during development to ensure accuracy of DNA replication in the rapidly dividing embryonic cells and to maintain genomic integrity in the mature organism. An enzyme involved in repair of replication errors generated on either normal or oxidatively damaged DNA templates, is the mammalian ortholog of the Escherichia coli MutY DNA glycosylase (MYH). We show that levels of MYH isoform, detected at the E14 embryonic stage, decrease during embryonic and neonatal rat development, while new isoforms appear and gradually increase in the neonate and adult brain. The temporally declining expression of embryonic MYH resembles the pattern of proliferating cell nuclear antigen (PCNA) decline during this period. Immunohistochemical analyses of the embryonic brain show that cells staining for MYH initially coincide with cells staining for PCNA. At later stages PCNA declines, while MYH is detected primarily outside the nucleus. MutY-like glycosylase activity for adenines misincorporated opposite oxidized guanines is detected in both, embryonic and adult brain extracts. Together, these findings suggest that in proliferating embryonic cells, MYH might be primarily involved in post replicative repair of nuclear DNA, whereas in post mitotic neurons, in the repair of mitochondrial DNA.