College of Michigan researchers have found {that a} worm generally used within the examine of biology makes use of a set of proteins in contrast to these seen in different studied organisms to guard the ends of its DNA.
In mammals, shelterin is a posh of proteins that “shelters” the ends of our chromosomes from unraveling or fusing collectively. Conserving chromosomes from fusing collectively is a vital job: chromosomes carry our physique’s DNA. If chromosome ends fuse, or in the event that they fuse with different chromosomes, the cell that homes these chromosomes dies.
However not all organisms use the identical sorts of proteins to kind shelterin. The worm C. elegans has been a strong mannequin for understanding many sorts of organic processes, says Jayakrishnan Nandakumar, U-M professor of molecular, mobile, and developmental biology.
Till not too long ago, nevertheless, scientists had not recognized the proteins that defend the double-stranded DNA ends of their chromosomes, known as telomeres. In 2021, Nandakumar’s collaborator Hiroki Shibuya and one other group independently found that proteins in C. elegans, known as TEBP-1 and TEBP-2, protected the worm’s telomeric ends.
Nonetheless, researchers hadn’t but unraveled all the mysteries of C. elegans shelterin. Proteins can have a number of elements to them, with every half performing a special perform, Nandakumar says. These elements are known as “domains,” that are named after the perform they carry out. Researchers weren’t certain which area allowed one TEBP-1 or TEBP-2 molecule to bind to a different copy of itself after which which area sure the proteins to chromosome DNA to assist defend it.
Now, Nandakumar and his staff have recognized the particular domains inside TEBP-1 and TEBP-2 proteins that enable them to carry out their organic capabilities. Their findings are revealed within the Proceedings of the Nationwide Academy of Sciences.
“There are totally different means to attain the identical finish (the pun is meant). In different phrases, due to our give attention to mammalian telomeres, we are inclined to bias ourselves in pondering ‘our method’ is the best method or the one technique to remedy issues within the cell,” he mentioned. “Nonetheless, the C. elegans instance reveals us that there are a number of methods to unravel the top safety downside and a few of them may be fairly totally different from how people do it. However so long as they’re efficient, they’re chosen for in evolution.”
Nandakumar says to think about chromosomes as a shoelace. The ends of your shoelace are coated with a tough plastic shell known as an aglet, which protects the lace from unraveling. People — and all mammals — have a sure set of proteins which might be the first elements of shelterin, the “aglet” of the chromosome.
“Consider these proteins because the plastic aglet that coats the ends of chromosomes to guard them from degradation and protect their integrity,” Nandakumar mentioned. “In C. elegans, TEBP-1 and TEBP-2 defend the chromosome ends.”
Now, these proteins, each in mammals and in C. elegans, want a technique to bind to one another after which to bind to the chromosome in order that they will successfully coat the chromosome finish. They do that utilizing what’s known as a dimerization area in addition to a DNA binding area half (when two an identical protein molecules bind collectively, researchers say they “dimerize”). In mammals, a site known as “TRFH” dimerizes these proteins, and a special area known as the “myb” area coats the chromosome ends.
Researchers hadn’t but recognized the C. elegans TEBP-1 or TEBP-2 dimerization and DNA binding domains as a result of they had been on the lookout for a protein in C. elegans that shared an identical amino acid sequence to the human protein domains — that’s, they had been on the lookout for a homolog of these proteins. However there wasn’t one.
As an alternative, C. elegans has three copies of one thing else, one thing that appears much like the myb area on the mammalian proteins. So the analysis staff known as them “myb-containing area,” or MCD 1, 2 and three. A single protein of TEBP-1 and TEBP-2, then, contains three segments: MCD1, MCD2 and MCD3.
The researchers additional discovered that solely MCD3 binds DNA. MCD1 and MCD2 appear like a DNA binding area, however as an alternative bind collectively molecules of TEBP-1 and TEBP-2. MCD1 in a single protein binds to MCD1 within the subsequent protein and MCD2 binds to MCD2, permitting the proteins to hyperlink as much as encompass the ends of the chromosomes.
To attach the protein complexes to the telomeres, MCD3 binds to the chromosome DNA. This entire protein is repeated across the total lengthy finish of the chromosome.
Nandakumar says that as a result of you’ll be able to carry out biochemistry and genetics readily with C. elegans, understanding the protein complexes that protects its telomeres will assist researchers use it as a mannequin organism for finding out telomere biology.
“Defending the telomeres of your DNA — each eukaryote has to do it, that means {that a} worm has to in some way determine that out. People need to determine it out. Yeast has to determine it out. It is a common downside,” Nandakumar mentioned. “Typically, in evolution, you’d use that very same technique in several species. If one thing is working, when you have an answer to an issue, why not reuse it? I feel the cool factor is, you’ll be able to have a number of options to the issue.”
