Photo Credit: Dr. Deborah Toiber / BGU
SIRT6 DNA structure

SIRT6 is the equivalent of a first responder to the site of DNA damage, the Toiber group at Ben-Gurion University of the Negev has discovered. A double strand break is the most serious type of DNA damage, because it can result in the loss of important genetic information, mistakes attaching the DNA back together, and inducing mutations in the DNA.

SIRT6, a protein, senses the broken DNA, arriving at the “scene” just 3 seconds after damage occurs. Once there, it starts alerting the surroundings, calling for reinforcements that will repair the broken DNA.

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Her findings were published recently in eLife.

Dr. Deborah Toiber and her group had previously discovered SIRT6’s role in repairing DNA damage, which ameliorates the effects of aging, cancer and neurodegenerative diseases, but this new discovery of SIRT6’s role as a sensor gives us the understanding of “starting over at Chapter 1 instead of jumping in at Chapter 3,” she says.

Toiber and others have been building a case around the importance of SIRT6 and this new discovery adds another layer of understanding.

“These findings lay the molecular groundwork for our future studies into SIRT6 and the crucial role it plays,” says Toiber.

There are only three other known sensors in the body that can detect broken strands of DNA. Now SIRT6 is the fourth. Importantly, these sensors seem to cooperate with each other to protect the DNA.

A lack of SIRT6 has been linked to shorter longevity in other studies of mammals from mice to beavers. Toiber’s previous research found that it was linked to the prevention of dementia in the elderly.

The driving force behind aging is the DNA damage that does not get repaired, Toiber explains. A lack of SIRT6 increases the rate of DNA damage.

The findings are also relevant for cancer, Toiber says. Chemotherapy causes DNA damage in the hopes of disrupting the proliferating cancer cells. Others have taken advantage of defects in DNA repair to kill cancerous cells.

The idea is to block any channel to repair the DNA in cancer cells, killing them in a more targeted way. It is possible that blocking SIRT6 could be used to block one more channel and increase the efficiency of chemotherapy.

The research was supported by grants from the Israel Science Foundation.

Dr. Toiber is a member of the Department of Life Sciences, Faculty of Natural Sciences at BGU. She was just awarded a prestigious European Research Council (ERC) Starting Grant to further her research into SIRT6 and the other sensors’ roles in DNA repair.

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