幹細胞研究と治療のジャーナル

概要

Differentiation of Embryonic Stem Cells and Oxidative DNA Damage / DNA Repair Systems

Hirano T and Tamae K

To maintain genomic integrity, cells are equipped with a defense capacity against DNA damage generated in genomic DNA. The avoidance of mutations in genomic DNA is especially critical for undifferentiated cells, such as Embryonic stem (ES) cells. Among the many factors damaging DNA, Reactive Oxidative Species (ROS) are crucial and unavoidable, and thus the roles of ROS in cell differentiation and cellular functions have been extensively studied. However, the biological significance of ROS generation in cell differentiation remains a matter of debate. Among the types of DNA damage due to ROS, 8-oxoguanine (8-oxo-Gua) has been well studied and is known to generate GC-to-TA point mutations in genomic DNA. We recently analyzed the differences in the resistance to 8-oxo-Gua generation between undifferentiated cells and their differentiated counterparts. Our studies indicated that undifferentiated cells were more resistant to 8-oxo-Gua generation, in comparison to differentiated cells. In this short review, we describe the relationship between ES cell differentiation and oxidative DNA damage / DNA repair systems, by summarizing our previous work and that of other researchers.