Featured Research

from universities, journals, and other organizations

You Can Be Replaced: Immune Cells Compensate For Defective DNA Repair Factor

Date:
September 8, 2008
Source:
Cell Press
Summary:
A new mouse model has provided some surprising insight into XLF, a molecule that helps to repair lethal DNA damage. The research suggests that although XLF shares many properties with well known DNA repair factors, certain cells of the immune system possess an unexpected compensatory mechanism that that can take over for nonfunctional XLF.

A new mouse model has provided some surprising insight into XLF, a molecule that helps to repair lethal DNA damage.

The research, published by Cell Press in the September 5th issue of the journal Molecular Cell, suggests that although XLF shares many properties with well known DNA repair factors, certain cells of the immune system possess an unexpected compensatory mechanism that that can take over for nonfunctional XLF.

Genetic instability can lead to multiple problems, including cell death and many forms of cancer. Therefore, it is absolutely critical for cells to have both the means to constantly survey genes for damage and the mechanisms to repair broken DNA. Currently, there are six well characterized classical non-homologous end-joining (C-NHEJ) factors that repair double strand breaks (DSBs) in mammalian cells.

Lymphocytes, a type of immune cell, use a kind of genetic shuffling called variable, diversity, joining V(D)J recombination. This gene shuffling occurs during lymphocyte development and helps to produce diverse immune system cells that can recognize all sorts of different foreign substances, called antigens, that might pose a threat to the organism. Previous work in mice has shown that deficiency of C-NHEJ factors results in a severely compromised immune system, because of incomplete V(D)J recombination, along with increased sensitivity to cellular ionizing radiation (IR) and genomic instability.

Some recent studies have suggested that XLF may serve as an additional C-NHEJ factor. "We know that XLF mutations in humans lead to decreased numbers of lymphocytes and a somewhat less severe form of immunodeficiency," says senior study author Dr. Frederick W. Alt from the Howard Hughes Medical Institute and Harvard Medical School. "While a role of XLF in C-NHEJ might explain lower than normal numbers of lymphocytes in human XLF-mutant patients, the reason for their relatively mildly impaired lymphocyte development is not clear."

To examine XLF function, Dr. Alt and colleagues generated and characterized XLF-mutant mice. XLF-deficient mouse cells were IR sensitive, had substantial genomic instability and displayed major defects in the ability to repair DSBs. Surprisingly, however, mature lymphocyte numbers were only modestly decreased in the XLF-deficient mice and developing B cells exhibited nearly normal V(D)J recombination. This finding was in direct contrast to results seen in previously characterized C-NHEJ-deficient mice. Further, on a tumor suppressor p53-deficient background, XLF-deficient mice were not prone to lymphomas as were C-NHEJ-deficient mice, even though they were just as likely to develop non-immune cell tumors.

The findings demonstrate that although the XLF-deficient mice share many characteristics associated with C-NHEJ-deficient mice, lymphocytes have a distinct developmental signature when it comes to XLF. "Together, our results implicate XLF as a C-NHEJ factor, but also indicate that developing mouse lymphocytes harbor cell type specific factors/pathways that compensate for absence of XLF function during V(D)J recombination," explains Dr. Alt.

The researchers include Gang Li, Frederick W. Alt, Hwei-Ling Cheng, James W. Brush, Peter H. Goff, Mike M. Murphy, Sonia Franco, Yu Zhang, and Shan Zha, of the Howard Hughes Medical Institute, The Children's Hospital, The CBR Institute of Biomedical Research, and Harvard Medical School, Boston, MA.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "You Can Be Replaced: Immune Cells Compensate For Defective DNA Repair Factor." ScienceDaily. ScienceDaily, 8 September 2008. <www.sciencedaily.com/releases/2008/09/080904144833.htm>.
Cell Press. (2008, September 8). You Can Be Replaced: Immune Cells Compensate For Defective DNA Repair Factor. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2008/09/080904144833.htm
Cell Press. "You Can Be Replaced: Immune Cells Compensate For Defective DNA Repair Factor." ScienceDaily. www.sciencedaily.com/releases/2008/09/080904144833.htm (accessed October 2, 2014).

Share This



More Plants & Animals News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Study Says Losing Sense Of Smell Can Indicate Death

Study Says Losing Sense Of Smell Can Indicate Death

Newsy (Oct. 2, 2014) Researchers found elderly adults with a poor sense of smell are more likely to die within five years. Video provided by Newsy
Powered by NewsLook.com
Dolphins and Turtles Under Threat in Pakistan

Dolphins and Turtles Under Threat in Pakistan

AFP (Oct. 2, 2014) The turtles and Dolphins of Pakistan's Indus river - both protected by law - are in a fight for their survival as man's activities threatens their futures. Duration: 02:29 Video provided by AFP
Powered by NewsLook.com
'Harvest Break' Endures in Maine Potato Fields

'Harvest Break' Endures in Maine Potato Fields

AP (Oct. 2, 2014) Educators and farmers are clinging to a tradition aimed at giving farmers much-needed help in getting potatoes out of the fields and into storage before the ground freezes in the nation's northeast corner. (Oct. 2) Video provided by AP
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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