Featured Research

from universities, journals, and other organizations

Allergic To Your DNA?

Date:
October 16, 2002
Source:
Cold Spring Harbor Laboratory
Summary:
Scientists have discovered that the presence of undigested DNA left over from dead cells can elicit an immune response in the fruit fly Drosophila, prompting researchers to question whether an analogous autoimmune response could be triggered in humans.

Scientists have discovered that the presence of undigested DNA left over from dead cells can elicit an immune response in the fruit fly Drosophila, prompting researchers to question whether an analogous autoimmune response could be triggered in humans.

Related Articles


The report is published in the October 15th issue of Genes & Development.

Apoptosis, or programmed cell death, is a critical biological process in which superfluous or potentially harmful cells undergo a series of genetic changes that ultimately result in the death of the cell, and its engulfment by a neighboring cell. Apoptosis is involved in a number of developmental and pathological processes, including embryonic digit sculpting and cancer prevention. The morphological changes that characterize apoptosis include nuclear DNA fragmentation and digestion– although research has shown that cells can undergo apoptosis without DNA degradation.

Dr. Shigekazu Nagata and colleagues at Osaka University in Japan set out to determine the biological significance of apoptotic DNA degradation.

Dr. Nagata's group used Drosophila as a model organism because apoptosis has been largely conserved throughout evolution from flies to mammals. Both fly and mammalian cells contain several DNase enzymes that specifically degrade DNA. During apoptosis, a DNase called CAD is released from its inhibitor, ICAD, and thereby activated to chop up DNA inside the dying cell. The engulfing cell also houses DNases, including DNase II enzymes inside the lysosome (a specialized cellular compartment where ingested material is digested) that are thought to play a role in apoptotic DNA degradation.

Dr. Nagata and colleagues generated strains of flies deficient in ICAD, DNase II, or both ICAD and DNase II in order to determine the relative contributions of each of these enzymes to apoptotic DNA degradation, and the physiological consequences of this process. The researchers found that ICAD-deficient flies also do not express CAD (ICAD is required for the normal folding of the CAD protein, and therefore its activity) and so no apoptotic DNA fragmentation occurred. The DNase II-deficient flies were able to fragment DNA inside the dying cells, but the fragmented DNA accumulated and activated an innate immune response. Finally, flies deficient in both ICAD and DNase II lacked apoptotic DNA degradation abilities and had an enhanced immune response, compared to the flies solely deficient in DNase II.

These findings lend important mechanistic insight into the process of apoptotic DNA disposal: They demonstrate that CAD is the primary DNase responsible for DNA fragmentation in dying cells, and that it functions in a separate pathway from DNase II. But the study is considered to be particularly interesting because the experimental results point to a previously unrecognized role for innate immunity in apoptotic DNA degradation.

"In mammals or humans, the activation of innate immunity causes the expression of various cytokines [cell signaling molecules]…that can induce inflammation or septic shock. If our results in Drosophila can be applied to mammalian systems, they suggest that DNA of the dying cells must be properly deposited. Otherwise, we will suffer from an immune response, like septic shock," explains Dr. Nagata. Further research is needed to determine if undigested apoptotic DNA can elicit an immune response in humans, but if so, this finding could open up a whole new list of possible culprits behind human autoimmune disease.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

Cold Spring Harbor Laboratory. "Allergic To Your DNA?." ScienceDaily. ScienceDaily, 16 October 2002. <www.sciencedaily.com/releases/2002/10/021016080002.htm>.
Cold Spring Harbor Laboratory. (2002, October 16). Allergic To Your DNA?. ScienceDaily. Retrieved February 27, 2015 from www.sciencedaily.com/releases/2002/10/021016080002.htm
Cold Spring Harbor Laboratory. "Allergic To Your DNA?." ScienceDaily. www.sciencedaily.com/releases/2002/10/021016080002.htm (accessed February 27, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Friday, February 27, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Amazon Keeps Its Green Thanks To The Sahara Desert

The Amazon Keeps Its Green Thanks To The Sahara Desert

Newsy (Feb. 25, 2015) Satellite data shows the Amazon rainforest supports its lush flora with a little help from Sahara Desert dust. Video provided by Newsy
Powered by NewsLook.com
Mayor Says District of Columbia to Go Ahead With Pot Legalization

Mayor Says District of Columbia to Go Ahead With Pot Legalization

Reuters - News Video Online (Feb. 25, 2015) Washington&apos;s mayor says the District of Columbia will move forward with marijuana legalization, despite pushback from Congress. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Marijuana Nowhere Near As Deadly As Alcohol: Study

Marijuana Nowhere Near As Deadly As Alcohol: Study

Newsy (Feb. 25, 2015) A new study says marijuana is about 114 times less deadly than alcohol. Video provided by Newsy
Powered by NewsLook.com
Fox With Horrifying Injury Rescued and Released Back Into the Wild

Fox With Horrifying Injury Rescued and Released Back Into the Wild

RightThisMinute (Feb. 25, 2015) This wounded fox knew what she was doing when she wandered into the yard of a nature photographer. The photographer got "Scamp" immediately in the hands of Wildlife Aid and she was released back into the wild in no time. Video provided by RightThisMinute
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