New DNA repair pathway

Nov 08, 2010

(PhysOrg.com) -- UC Davis researchers have found a new pathway for repairing DNA damaged by oxygen radicals. The results are published this week in the journal Proceedings of the National Academy of Sciences.

"This new inducible pathway gives cells greater capacity to repair oxidative damage," said Peter Beal, professor of chemistry at UC Davis and senior author of the paper.

As part of its , the body's immune system produces oxygen radicals, or reactive oxygen species, to kill bacteria, parasites or tumors. But , for example in the gut, has been linked to cancer, said co-author Professor Sheila David, also of the Department of Chemistry.

Oxygen radicals are strongly linked to cancer and aging and are also formed during metabolism and upon exposure to environmental toxins and radiation. Understanding more about how this damage can be repaired could lead to a better understanding of the causes of some cancers.

Oxygen radicals can react with the four bases that make up the "letters" of DNA -- A, C, G and T -- so that the "spelling" of genes gets changed. The accumulation of spelling errors (called mutations) can lead to cancer.

David's laboratory studies an enzyme called NEIL1 that detects and repairs these aberrant or damaged bases before changes in the genome become permanent.

Beal's group works on RNA editing. The first step in turning a gene into a protein is to make a copy of the DNA in RNA. This is then translated into the chain of that makes up a protein. In some cases, this RNA is "edited" between the transcription from DNA and the translation into protein.

At a conference last year, Beal -- who happens to be David's husband -- spotted NEIL1 among a list of genes that had just been discovered to be subject to RNA editing, and passed the news on to David.

On investigation, they found that NEIL1's messenger RNA is edited by an enzyme called ADAR1. In that editing, one of the chains of amino acids that make up NEIL1 changes from lysine to arginine, causing a slight, but noticeable, change in the structure of the protein.

Using a cell line derived from nerve cells, the team found no editing of NEIL1 RNA in resting cells. But when the cells were treated with interferon, which is produced during inflammation and to fight off viruses, the cells started making ADAR1 and editing NEIL1.

"The interferon-treated cells had two forms of the NEIL1 protein, one with lysine and one with arginine," Beal said.

NEIL1 can fix a number of different damaged DNA bases that form when normal DNA bases are attacked by oxygen radicals. Beal and David found that the two different forms of NEIL1 had different abilities to act upon the damaged DNA bases: the basic, lysine version had a broader range but lower activity, while the edited, arginine form had higher activity but was effective against a more limited range of targets. That might give the cell more flexibility in responding to DNA damage.

Beal and David believe that the whole system works something like this: Inflammation creates , which damage DNA, which is repaired by NEIL1. Inflammation also generates interferon, which induces ADAR1, which then edits NEIL1 to produce the more active, specific form to cope with more severe types of DNA base damage.

Explore further: Four billion-year-old chemistry in cells today

Related Stories

Research Highlights Protein's Role in Cell Health

Jun 09, 2010

(PhysOrg.com) -- Simple, but necessary human actions like breathing oxygen can damage our cells' DNA. If left unrepaired, this damage can cause multiple mutations and the type of unregulated cell division common in cancerous ...

Cells can read damaged DNA without missing a beat

Feb 09, 2010

Scientists have shown that cells' DNA-reading machinery can skim through certain kinds of damaged DNA without skipping any letters in the genetic "text." The studies, performed in bacteria, suggest a new mechanism that can ...

Recommended for you

A new approach to creating organic zeolites

Jul 24, 2014

Yushan Yan, Distinguished Professor of Engineering at the University of Delaware, is known worldwide for using nanomaterials to solve problems in energy engineering, environmental sustainability and electronics.

User comments : 4

Adjust slider to filter visible comments by rank

Display comments: newest first

kevinrtrs
1 / 5 (7) Nov 09, 2010
Beal and David believe that the whole system works something like this: Inflammation creates oxygen radicals, which damage DNA, which is repaired by NEIL1. Inflammation also generates interferon, which induces ADAR1, which then edits NEIL1 to produce the more active, specific form to cope with more severe types of DNA base damage

So just how did this evolve? Seems like a lot of foreknowledge is required before this could happen. And since random mutations do not have this foreknowledge, just how DID it happen? Couple this one tiny little bit with the millions of other little bits of foreknowledge required and the CHANCE occurrence of man from molecules becomes terribly, vanishingly small.
Man did NOT evolve from a lower single-celled form but was fully formed at the beginning.
mgb
5 / 5 (2) Nov 09, 2010

Man did NOT evolve from a lower single-celled form but was fully formed at the beginning.


lol
Skeptic_Heretic
5 / 5 (5) Nov 09, 2010
So just how did this evolve? Seems like a lot of foreknowledge is required before this could happen. And since random mutations do not have this foreknowledge, just how DID it happen?
How do people win the lottery without knowing exactly which numbers are going to be drawn.

It's an amazing thing that can't ever happen, ever. The lottery must be rigged.
Man did NOT evolve from a lower single-celled form but was fully formed at the beginning.
And he used to ride dinosaurs to the quarry and enjoy rock bowling after work.
(LOL)
Skultch
5 / 5 (4) Nov 09, 2010
Kevinrtrs, you are the worst of this site's trolls. You have absolutely NO chance at convincing anyone. Why are you here?