Endeavors magazine: The trouble with timeless and tipin

The trouble with timeless and tipin

by Mark Derewicz

These proteins help DNA repair but let cancer survive.

The human body’s natural effort to prevent skin cancer may also hinder cancer treatments, a twist of fate that pathologist William Kaufmann and his collaborators uncovered.

Kaufmann’s team demonstrated that two cellular proteins—Tipin and Timeless—help slow the rate of DNA replication. This slowdown gives cells additional time to repair DNA that ultraviolet radiation has damaged. It is this damage, or cellular mutation, that if left untreated could lead to skin cancer, a disease that affects one million Americans each year.

The slowdown of DNA replication, of course, is a good thing; it’s nature’s way of protecting the body from cancerous growths.

“But the protective response may make some cells more resistant to certain types of cancer therapy, such as radiation treatment and chemotherapeutic agents, which work by inducing the cancer cell to die,” Kaufmann says. “If a cancer cell is given this additional time to recover from treatment, it may be able to survive the treatment, much to the detriment of the patient.”

UNC’s team includes several scientists. Pathologist Paul Chastain developed a way to label DNA molecules with fluorescent colors so scientists can study what happens to different DNA molecules under various conditions. Former UNC biochemist Keziban Unsal-Kacmaz created chemical reagents that reduce the effects of Timeless and Tipin within cell nuclei. As a team, the researchers learned what happened to DNA when Timeless and Tipin were suppressed in cells that had been exposed to very low doses of ultraviolet radiation. If Tipin’s effect is suppressed, then the effects of Timeless are completely stopped; if Timeless is taken out, then Tipin’s power to slow replication is reduced, but not completely eradicated. But if the two proteins are left to their own devices, they can help slow down or stop DNA replication, allowing cells to repair damage and resist cancer treatment.

“These are the kinds of things we would want to inhibit when applying chemotherapy or radiation to cancer cells,” Kaufmann says, “because taking out this system will make killing cancer cells more effective.”

William Kaufmann, professor of pathology and lab medicine in the School of Medicine, received funding from the National Institute of Environmental Health Sciences and the National Cancer Institute.

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welcome:

from the editor.

overview:

in print:

endview:

art for adoption.

fine print:

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