
<ArticleTitle><prot>hMYH</prot> cell cycle-dependent expression, subcellular localization and association with replication foci: evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs.</ArticleTitle>
<AbstractText>The human <prot>MutY</prot> homolog, <prot>hMYH</prot>, is an adenine-specific DNA glycosylase that removes adenines or 2-hydroxyadenines mispaired with guanines or 8-oxoguanines. In order to prevent mutations, this activity must be directed to the newly synthesized strand and not the template strand during DNA synthesis. The subcellular localization and expression of <prot>hMYH</prot> has been studied in serum-stimulated, proliferating MRC5 cells. Using specific antibodies, we demonstrate that endogenous <prot>hMYH</prot> protein localized both to nuclei and mitochondria. <prot>hMYH</prot> in the nuclei is distinctly distributed and co-localized with BrdU at replication foci and with <prot>proliferating cell nuclear antigen</prot> (<prot>PCNA</prot>). The levels of <prot>hMYH</prot> in the nucleus increased 3- to 4-fold during progression of the cell cycle and reached maximum levels in S phase compared to early G(1). Similar results were obtained for <prot>PCNA</prot>, while there were no notable changes in expression of 8-oxoguanine glycosylase or the human <prot>MutT</prot> homolog, <prot>MTH1</prot>, throughout the cell cycle. The cell cycle-dependent expression and localization of <prot>hMYH</prot> at sites of DNA replication suggest a role for this glycosylase in immediate post-replication DNA base excision repair.</AbstractText>
