According to a study a tumor-suppressing protein, called BRIT1, gives signal to cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.
Led by scientists at The University of Texas M. D. Anderson Cancer Center, the study showed that BRIT1 connects with another protein complex to relax DNA's tight packaging at the site of the damage.
Advertisement"Relaxing this barrier allows two different DNA repair pathways greater access to the damage, preventing flawed DNA from being passed on as the cell divides, which causes genomic instability leading to cancer," Nature magazine quoted senior author Dr. Shiaw-Yih Lin as saying.
BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines and researchers had earlier shown that it plays a key role in early detection of DNA damage.
First author Dr. Guang Peng said that chromosomes are made of DNA that is tightly intertwined with proteins called histones to form chromatin, which is a very condensed structure that forms a natural barrier inhibiting access to genes.
ATP-dependent chromatin remodeling is a fundamental mechanism used by cells to relax chromatin in DNA repair, but the detailed molecular mechanism by which it is recruited to DNA lesions in response to damage signalling is not known until now.
"Our studies demonstrate a novel mechanism by which BRIT1 recruits chromatin remodeling factors to DNA lesions to facilitate chromatin relaxation and DNA repair," said Peng.
After conducting a series of lab experiments, scientists showed that BRIT1 accomplishes this by enhanced binding to a known chromatin remodeling complex called SWI-SNF when a specific site on the complex is phosphorylated.
BRIT1 also maintains the relaxation factor at the damage site.
They demonstrated that normal BRIT1 aids repair of double-stranded DNA breaks by allowing access to two repair pathways: homologous recombination (HR) and non-homologous end joining (NHEC).
Peng said that the findings hold potential to treat cancer cells lacking BRIT1 with PARP inhibitors-drugs that specifically kill HR-deficient cancer cells.
The study has been published online in Nature Cell Biology.
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