UT Medical Branch Researchers Discover NEIL1 “Cowcatcher” enzyme fixes single-strand DNA

NEIL1 enzymeDuring the process of replication (creating daughter cells), cells have to open the double-stranded helical structure of DNA.  This forms two single-strands of DNA, which exposes the inner bases to reactive oxygen species.  These reactive oxygen species can cause changes in the genetic information.  If this process is left unchecked, mutations quickly add up, producing a number of genetic errors generating disorders such as cancer, accelerated aging and neurodegenerative diseases.  Fortunately, evolution has developed a way to repair these mutations in the single-stranded genome.  Recently, researchers at the University of Texas Medical Branch at Galveston (UTMB) have discovered how this process works.

During replication, the double-stranded DNA separates in a manner that is somewhat analogous to the opening of a zipper.  As the DNA opens, it exposes strings of four uniformly spaced bases attached to each single strand of DNA.  Downstream of this, each of these strands is straddled by an advancing replication complex of proteins replicating or copying the single strand back into a double strand.  The problem with this process is located between these new double strands that are being formed and the open zipper part.  This is where DNA is most likely to become damaged and removal of a damaged base would ultimately cause the strand to break.

Scientists have known that there is an enzyme known as NEIL1 that recognizes single-stranded DNA, and they also knew that it was associated with the replication complex.  Researchers at UTMB have done in vitro experiments that have brought to light that NEIL1 rides in front of the replication complex looking for single-strand DNA damage.

According to Muralidhar Hegde, UTMB assistant professor and lead author on the paper, “As soon as it encounters the base damage, NEIL1 binds to the damage site and flags it, and replication cannot continue.  The replication machinery stalls and then regresses, and the two strands come back together which allows repair of the damaged base in duplex DNA, replacing the damaged base with the appropriate normal base”.  Once that takes place, the DNA zipper begins opening again.  Hegde goes on further to say, “The replication machinery comes back and it continues, so we have NEIL1 both looking at what is ahead and signaling to the back.”

Check out the video below for an overview of DNA Structure and Replication:

Sankar Mitra, senior author of this paper, provides an analogy by saying that NEIL1 is like a “cowcatcher” enzyme meaning that he is comparing it to the structure on the front end of an steam locomotive that is used to clear animals and debris off train tracks.  Mitra goes on further to say,  “Basically, the replication train is coming and the cowcatcher is in front to see if any damage is present. If it finds such damage, the train moves backward, you repair it, and the train starts moving forward again. Of course, that’s a simplification of a very complex chemical reaction — an exquisitely controlled and regulated process, and one that’s very important to maintaining the integrity of the genome.”

Photo from wikipedia.org

About Chris Comish

Chris Comish is the Publisher, President, and CEO of BioNews Texas. He is an influencer in the Texas biotech industry and guides the editorial and content direction of the publication.
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