PgmNr Y3015: Response of quiescent cells to exogenous DNA damage.

Authors:
L. J. Long 1 ; J. S. Welty 1,2 ; M. A. Osley 1


Institutes
1) University of New Mexico School of Medicine, Albuquerque, NM; 2) University of Pittsburgh, Pittsburgh, PA.


Keyword: Cell Cycle/Growth Control/Metabolism

Abstract:

Under certain conditions, such as nutrient deprivation, cells exit the cell cycle and enter G0, a state of quiescence. Quiescent cells are viable but non-growing and can re-enter the cell cycle when appropriate stimuli are provided. Quiescence is an important feature of adult stem cells, where it provides a pool of cells for self-renewal or differentiation into appropriate cell lineages. Quiescent cells must respond to exogenous stresses such as DNA damage so that deleterious mutations are not transmitted to progeny upon differentiation. Our data show that quiescent cells are more sensitive to UV irradiation when compared to growing cells. We find that the majority of UV lesions are removed from quiescent cells before these cells re-enter the cell cycle. Moreover, we observe that the frequency of UV-induced mutations is significantly higher in quiescent cells than in G1 arrested cells. We are currently using genetic, molecular, and genomic approaches to investigate the hypothesis that UV induced lesions are directly repaired in G0 cells through the gap-filling activity of mutagenic translesion DNA polymerases.