New UTSA research shows stem cells do not respond to DNA damage

By Christi Fish
Public Affairs Specialist

(Oct. 12, 2009)–Led by UTSA Associate Professor Christopher Navara, a team of researchers has demonstrated that unexpectedly the damage checkpoint in the cell cycle slows but does not prevent damaged human embryonic stem (ES) cells from replicating. The team’s findings, published in the journal Stem Cells, are significant because they demonstrate that stem cell replication can result in daughter cells with damaged DNA.

“ES cells are highly sensitive to DNA damage,” said Navara, an associate professor of biology in the College of Sciences and a member of UTSA’s San Antonio Institute for Cellular and Molecular Primatology. “In this study, we irradiated ES cells to intentionally damage their DNA. Then, we observed how the cells detected and responded to the damage during replication by monitoring a protein called ATM, one of the first sensors for DNA damage. We had expected to see the checkpoint recognize the damaged cells, leading them to die, but that did not happen.”

To replicate, all cells must complete a four-phase process called the cell cycle. The four phases of the cycle are Gap 1 (G1), in which the cell prepares its DNA to be copied; Synthesis (S) in which the DNA is copied; Gap 2 (G2) in which the cell prepares to be divided into two cells; and Mitosis (M) or cell division. Several checkpoints allow the cell to pause and assess whether each phase was completed properly. If, at a checkpoint, the cell is ready to enter the next phase, it proceeds. If the cell detects that something is wrong, it arrests and attempts to fix the problem. If it cannot fix the error, the cell dies.

When Navara’s research team irradiated ES cells in the laboratory to damage their DNA, they observed that instead of stopping and dying at the G1 checkpoint as damaged cells should, they continued through the S and G2 (second and third) phases of the cell cycle. At the checkpoint following the G2 phase the cells eventually arrested. There, the researchers observed a pause in the cell cycle lasting 16 hours after irradiation. But, instead of dying at the checkpoint, the damaged ES cells continued through the rest of the cell cycle after the 16-hour pause, progressing despite unrepaired DNA damage.

This research has critical implications for the understanding of early human development and potentially of how cancer progresses. The next step in the research is to determine how these errors happen and why.

DNAWellnessinfo.com Resource:  http://www.utsa.edu/today/2009/10/stemcells.cfm