Protein that helps summon DNA repair teams to fix cancer-causing defects identified
20 Jun 2009, 1522 Hrs

Add comment          Mail          Print          Write to Editor

London, June 20 A tumour-suppressing protein, called BRIT1, gives signal to cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access, according to a study.

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.

"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 remodelling 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 remodelling 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. (ANI)

Related Latest

Snowstorm: Rescue teams recover ten bodies from Rohtang Pass Beach ball that denied Liverpool victory donated to UK football museum Scientists find "predator" corals that eat jellyfish Soon, "green" tires that boost mileage and cut CO2 emissions Now, smartphone app that illuminates power consumption A show that will go into people's past lives 'Scrudle': the newest utensil that scrapes every last morsel from saucepans Simple, low cost method helps locate landmines Soon, a spray that can prevent premature ejaculation Molecular trigger that helps prevent aging and disease found

Related Latest

Warnie says 'Pup' Clarke is his new bunny in 20-20 match Assam bomb blast death toll rises to seven (Update Assam blast) Windies won't wilt against Aussies, says coach Williams Central Excise, Customs official protest in Delhi for better pay Teenager charged for mutilation murder of Brit Indian Orissa Govt orders heavy security deployment in Korapat District Ferguson's overhaul plan puts greats under scrutiny Arrest warrant issued against two ministers in Karzai's cabinet Former Australian cricket stars question Clarke's capacity to captain Headley always felt pulled between East and West: Investigators

• Windies won't wilt against Aussies, says coach Williams
• Assam bomb blast death toll rises to seven (Update Assam blast)
• Orissa Govt orders heavy security deployment in Korapat District
• Warnie says 'Pup' Clarke is his new bunny in 20-20 match
• Central Excise, Customs official protest in Delhi for better pay

• भारतीय क्रिकेट की मजबूत दीवार
• कंगारूओं के आगे ढेर, चीतों से कैसे मुकाबला करेंगें शेर
• Reducing greenhouse gases may not be enough to slow global warming
• बीकानेर महापौर चुनावः एक विश्लेषण
• Deepawali: The Festival Of Lights