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RASSF1A suppresses the activated K-Ras-induced oxidative DNA damage
Authors:Seon Ho Park  Jung Jin Kim  Jin Sil Chung  So Ra Lee  Gi Young Lee  Hyung Jung Kim  Young Do Yoo
Affiliation:aLaboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705, Republic of Korea;bDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul 135-270, Republic of Korea
Abstract:The mutant K-Ras elevates intracellular reactive oxygen species (ROS) levels and leads to oxidative DNA damage, resulting in malignant cell transformation. Ras association domain family 1 isoform A (RASSF1A) is known to play a role as a Ras effector. However, the suppressive effect of RASSF1A on K-RasV12-induced ROS increase and DNA damage has not been identified. Here, we show that RASSF1A blocks K-RasV12-triggered ROS production. RASSF1A expression also inhibits oxidative DNA damage and chromosomal damage. From the results obtained in this study, we suggest that RASSF1A regulates the cellular ROS levels enhanced by the Ras signaling pathway, and that it may function as a tumor suppressor by suppressing DNA damage caused by activated Ras.
Keywords:K-Ras   RASSF1A   ROS   DNA damage
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