Featured Research

from universities, journals, and other organizations

Tumor-suppressor Recruits Help To Overcome A Barrier And Fix Cancer-causing Defects

Date:
July 1, 2009
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
Like a mechanic popping the hood of a car to get at a faulty engine, a tumor-suppressing protein allows cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.

Like a mechanic popping the hood of a car to get at a faulty engine, a tumor-suppressing protein allows cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.

Reporting online at Nature Cell Biology this week, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center shows 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," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in M. D. Anderson's Department of Systems Biology.

BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines. Lin and colleagues previously showed that the protein plays a key role in early detection of DNA damage.

Chromosomes are made of DNA that is tightly intertwined with proteins called histones to form chromatin. Chromatin is a very condensed structure that forms a natural barrier inhibiting access to genes, said first author Guang Peng, Ph.D., a post-doctoral fellow in Systems Biology. 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 signaling has been largely unknown.

BRIT1 summons help

"Our studies demonstrate a novel mechanism by which BRIT1 recruits chromatin remodeling factors to DNA lesions to facilitate chromatin relaxation and DNA repair," Peng said.

A series of lab experiments 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.

The team showed 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).

DNA repair efficiency dropped by between 40 and 60 percent in cells with BRIT1 knocked down that were then exposed to ionizing radiation, allowing many damaged cells to divide and pass on their genetic defects.

Potential for cancer treatment

Having shown that BRIT1 deficiency impairs HR repair, Peng said one solution the team is examining is to treat cancer cells lacking BRIT1 with PARP inhibitors, drugs that specifically kill HR-deficient cancer cells.

BRIT1 mutations are known to cause a neurological condition called primary microcephaly, in which the brain develops to only one third of normal size. The team showed that in experiments using cells derived from primary microcephaly patients that BRIT1 dysfunction may specifically contribute to development of the neurological disease by failing to bind to SWI-SNF to relax chromatin.

The research was funded by grants from the National Cancer Institute and an American Cancer Society Research Scholar Award.

Co-authors with Lin and Peng are: Eon-Kyoung Yim, Hui Dai, Mei-Ren Pan, Ph.D., Ruozhen Hu, all of M. D. Anderson's Department of Systems Biology; Hu is also a student in the University of Texas Graduate School of Biomedical Sciences; Andrew Jackson, Ph.D., of MRC Human Genetics Unit, Western General Hospital in Edinburgh; Ineke van der Burgt, Ph.D., Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, Netherlands; Kaiyi Li, Ph.D., Department of Surgery, Baylor College of Medicine.


Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Tumor-suppressor Recruits Help To Overcome A Barrier And Fix Cancer-causing Defects." ScienceDaily. ScienceDaily, 1 July 2009. <www.sciencedaily.com/releases/2009/06/090619112327.htm>.
University of Texas M. D. Anderson Cancer Center. (2009, July 1). Tumor-suppressor Recruits Help To Overcome A Barrier And Fix Cancer-causing Defects. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2009/06/090619112327.htm
University of Texas M. D. Anderson Cancer Center. "Tumor-suppressor Recruits Help To Overcome A Barrier And Fix Cancer-causing Defects." ScienceDaily. www.sciencedaily.com/releases/2009/06/090619112327.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins