High fidelity: SLU researcher finds keys to genome integrity

IMAGE:Saint Louis University research team: Shivasankari Gomathinayagam, Alessandro Vindigni, Monica Carron, Megan Fabry, Denisse Carvajal, Galyna Yakymechko, Matteo Berti, Saravanabhavan Thangavel. view more

Credit: Saint Louis University

ST. LOUIS - Maintaining the stability and the correct sequence of our genetic information is vital to the accurate transmission of our genetic code. However, in the course of replicating, our DNA frequently runs into roadblocks, arising from both internal and external sources, that threaten the fidelity of our genetic information. The accurate processing of these roadblocks is paramount to genome integrity. Defects in this process can lead to cancer, genetic problems and premature aging.

In a research paper published in the Journal of Cell Biology, Alessandro Vindigni, Ph.D., professor in the Edward A. Doisy Department of Biochemistry and Molecular Biology at Saint Louis University, shares a discovery that explains how cells use a process called replication fork reversal in order to deal with these roadblocks and transmit accurate genetic data.

Lesions in DNA can occur as often as 100,000 times per cell per day. They can be the result of normal metabolic activities, like free radicals, as well as exposure to environmental factors such as UV radiation, X-rays and chemical compounds.

Improper repair of DNA lesions can lead to mutations, abnormal chromosome structures, or loss of genetic information that in turn can cause premature aging, cancer, and genetic abnormalities.

Depending on the degree of genome instability, these alterations will determine whether a cell survives, goes into a growth-arrest state, or dies.

If the cell's replication machinery collides with the lesion, a strand break can occur.

"If these strands are not repaired properly, the cell may simply die," Vindigni said. "Or, growth may be permanently interrupted.

"Or, a serious lesion may be tolerated and the cell will continue to replicate. This may or may not be a good decision, as this can lead to cancer. It is the degree of genomic instability caused by the lesion that will determine whether the cell will survive."

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High fidelity: SLU researcher finds keys to genome integrity