위장관의 유전자 손상복구 인자에 대한 연구

Abstract

DNA mismatch repair (MMR), as a member of DNA damage repair system, e mainteins genomic stability and suppresses tumorigenesis via the function in repair of post-replicative DNA errors. Chronic oxidative stress is generally believed to be a major etiologic factor in the aging process. Not only influences cellular signaling and oxidation of cellular proteins and lipids, but reactive oxygen species (ROS) have powerful effect, multiple damages, on both nuclear and mitochondrial genomes. This serious celluar injuries are mostly repaired via maily DNA base excision repair pathway and MMR. It is relatively well-known that 8-oxoG-DNA glycosylase (OGG1) and AP-endonuclease (APE1) in the initial steps of DNA base excision repair, but not in MMR. So in order to ascertain the physiological role of the MMR in aging, we have investigated the changes of MMR proteins, Msh2 and Msh6, in postnatal aging colon of rat. We found that the amount of protein level of MMR was decreased with age in colon. This data is also confirmed that the immunostaining of mucosal epithelium and intestinal gland was weakened in aged rat colon by the immunohostochemical approach. Therefore, we propose that dysfunctional MMR with age may be associated with the increasing DNA damage and tumorigenesis