Scientists Identify Critical Protein That Helps Mend Damaged DNA

A protein named CtIP plays an essential role in the DNA damage "signal-to-repair" conversion process, according to scientists at the Salk Institute for Biological Studies.

The discovery could be a big step towards solving the complex puzzle of how damaged DNA is repaired.

"Being able to repair damaged DNA is extremely important; the cell has to know when it has received this type of damage and respond appropriately. Failure to do so can have disastrous consequences," explained Dr. Tony Hunter.

The DNA in our cells is under constant attack from reactive chemicals generated as byproducts of cellular metabolism.

In addition, it gets damaged via x-rays, ultraviolet radiation from the sun, and environmental carcinogens such as tobacco smoke.

Because of this continuous bombardment, some studies have estimated that the DNA in a single human cell gets damaged over 10,000 times every day.

If not repaired properly, the damage leads to mutations, which over time can cause cancer.

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"As a result, individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer," said first author Dr. Zhongsheng You.

DNA consists of two intertwined strands so that when the DNA is broken, two ends are revealed, one from each strand.

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In order to repair the DNA break, one strand is trimmed away-or resected-like a loose thread, leaving only the second strand.

The exposed strand then searches for a copy of itself (located on its sister chromosome), and "photocopies" past the broken region, repairing the DNA and zipping itself back up.

In yeast, CtIP is required for resection of the broken end, and since it is also recruited to sites of DNA damage in human cells, the researchers wanted to know whether CtIP plays a similar role there.

For the study, they depleted CtIP from human cells and caused DNA damage.

Without the CtIP, they discovered, the cells could no longer trim back the damaged DNA strands, which brought the whole repair process to an abrupt halt.

"It looks like CtIP recruitment is a very important control point in the DNA repair process. Once CtIP is recruited, resection and repair begin, so regulating CtIP recruitment is one way to regulate DNA repair itself," said You.

By testing small portions of the protein, they found that a region in the central part of CtIP helps recruit the protein. They named this region the "damage recruitment" (DR) domain.

The authors believe that exposure of CtIP 's DR domain and its recruitment to the site of DNA damage triggers a chain reaction that results in DNA repair, and they now want to understand exactly what CtIP does to start the DNA repair process.

In the long term, the team hopes that a better understanding of the DNA damage pathway may provide clues for cancer treatment in the future.

The study has been published in the latest issue of Molecular Cell.

Source-ANI
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