DNA repair in normal stem cells

Abstract

Stem cells are self-renewing cells with the ability to differentiate into one or more somatic cell types. Pluripotent stem cells (PSCs) can form any type of somatic cell and play essential roles during development, whereas multipotent stem cells produce a limited number of closely related cell types and are responsible for tissue homeostasis during an organism's lifetime. It is essential for stem cells to maintain genomic integrity, as alterations of their DNA sequence would be transmitted to daughter cells. This might affect developmental processes, tissue cellularity and function, and lead to aging and malignant transformation. The fast pace of the cell cycle in PSCs exposes them to the risk of accumulation of replication errors, whereas the long life of multipotent stem cells predisposes them to accumulation of mutations. PSCs employ several mechanisms to minimize mutational burden, such as low mitochondrial activity and reactive oxygen species (ROS) production, high activity of efflux pumps, expression of telomerase, efficient DNA repair, as well as triggering apoptosis at a lower threshold than other cell types. Quiescence of multipotent stem cells may minimize chances of accumulation of replication errors, and protect them from oxidative stress due to low metabolic activity, mitochondrial respiration, and ROS production. However, quiescence may act as a double-edged sword, since resting in the G0 phase of the cell cycle limits the choice for DNA double strand break repair to error prone non-homologous end joining.