title: Cell cycle adaptations and maintenance of genomic integrity in embryonic stem cells and induced pluripotent stem cells.
abstract: Pluripotent stem cells have the capability to undergo unlimited self-renewal and differentiation into all somatic cell types. They have acquired specific adjustments in the cell cycle structure that allow them to rapidly proliferate, including cell cycle independent expression of cell cycle regulators and lax G(1) to S phase transition. However, due to the developmental role of embryonic stem cells (ES) it is essential to maintain genomic integrity and prevent acquisition of mutations that would be transmitted to multiple cell lineages. Several modifications in DNA damage response of ES cells accommodate dynamic cycling and preservation of genetic information. The absence of a G(1)/S cell cycle arrest promotes apoptotic response of damaged cells before DNA changes can be fixed in the form of mutation during the S phase, while G(2)/M cell cycle arrest allows repair of damaged DNA following replication. Furthermore, ES cells express higher level of DNA repair proteins, and exhibit enhanced repair of multiple types of DNA damage. Similarly to ES cells, induced pluripotent stem (iPS) cells are poised to proliferate and exhibit lack of G(1)/S cell cycle arrest, extreme sensitivity to DNA damage, and high level of expression of DNA repair genes. The fundamental mechanisms by which the cell cycle regulates genomic integrity in ES cells and iPS cells are similar, though not identical.
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA. momcilovico@upmc.edu
authors.forename: Olga
authors.initials: O
authors.lastname: Momčilović
authors.forename: Christopher
authors.initials: C
authors.lastname: Navara
authors.forename: Gerald
authors.initials: G
authors.lastname: Schatten
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000502:physiology*; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*