Researchers locate control center for DNA breaks during cell division – Phys.Org

April 17, 2017 by Stephanie Dutchen Cell nuclei light up in the reproductive organ of a worm. Modifying a particular protein (green) by adding a phosphate group (red) sends a signal to stop breaking DNA. Credit: Priah Nadarajan

Breaks in DNA can wreak havoc in the body, giving rise to cancer and other health problems. Yet sometimes cells rupture their own DNA for a good reason.

During meiosis, when cells divide to become sperm and eggs, making and repairing DNA breaks helps lock together pairs of chromosomes so they can exchange genetic material and continue on their reproductive journey.

But even "good" breaks need to be controlled before they get out of hand, and so, once chromosomes have been paired up, something tells the DNA-snapping machinery to shut down. What exactly gives the command, however, has eluded researchersuntil now.

Studying the reproductive organs of tiny worms called Caenorhabditis elegans, a team of Harvard Medical School scientists has identified a trio of proteins that staff the DNA-break control center. If the same proteins operate the controls in humans, the researchers say, the finding could suggest new ways to rein in runaway DNA breaks throughout the body to avert cancer, infertility, miscarriages and birth defects.

Genetics professor Monica Colaicovo, postdoctoral fellow Saravanapriah Nadarajan and colleagues reported their discoveries in the journal eLife.

The team found that a pair of enzymes, polo-like kinases 1 and 2, sense when two chromosomes attach at a DNA break site. The enzymes then begin to sound the "no more breaks needed" alarm by sticking a chemical tag onto proteins called SYP-4. SYP-4 is part of a zipper-like structure that holds chromosome pairs together during meiosis.

The researchers watched through a microscope as a wave of this tagging, known as phosphorylation, started at the break site, shown above in green, and spread out, shown in pink, in both directions along the zipper until it reached the ends of the chromosomes.

"We think this makes the chromosomes less accessible to the machinery that makes the DNA breaks," said Colaicovo.

The researchers discovered that phosphorylation not only blocks additional DNA breaks, it also helps stabilize the zipper.

"Having a more stable zipper probably helps disseminate the 'stop' signal," said Colaicovo.

Further experiments showed that "when you mess up the ability to modify SYP-4, the cells never stop making double-strand breaks," Colaicovo added. As a result, worms with uncontrolled DNA breaks had problems with their eggs that led to infertility or sterility, Nadarajan revealed.

Having answered a fundamental question about how DNA breaks are controlled, the researchers are now wondering whether their discoveries apply to humans.

A look at sperm and egg precursor cells in mice and humans turned up a promising lead: Proteins that form the equivalent zipper are similarly phosphorylated by polo-like kinases.

Explore further: Researchers find chemical tag that locks chromosomes together during meiosis

More information: Saravanapriah Nadarajan et al. Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop, eLife (2017). DOI: 10.7554/eLife.23437

Journal reference: eLife

Provided by: Harvard Medical School

Chromosomes perform an intricate dance inside the nuclei of cells undergoing meiosis (dividing into sperm and eggs). One stumble can lead to infertility, miscarriage, birth defects or tumor formation.

Where would we be without meiosis and recombination? For a start, none of us sexually reproducing organisms would be here, because that's how sperm and eggs are made. And when meiosis doesn't work properly, it can lead to ...

A team of researchers from the biology department at TU Darmstadt has discovered that the processes for repairing DNA damage are far more complex than previously assumed. The ends of breaks in the double helix are not just ...

Monica Colaicovo has made a career of studying meiosis, the type of cell division that produces eggs and sperm. Meiosis is essential for healthy reproduction. Chromosomal abnormalities resulting from errors in meiosis cause ...

Crossovers and double-strand DNA breaks do not occur randomly on yeast chromosomes during meiosis, but are greatly influenced by the proximity of the chromosomes telomere, according to research in the laboratory of Whitehead ...

The genetic information we receive from our parents in the form of chromosomes are mosaics assembled from the two copies of chromosomes each parent has. How such cutsor breaksin our genetic material are repaired is ...

Scientists at the University of California, Davis have discovered that DNA sequences thought to be essential for gene activity can be expendable. Sequences once called junk sometimes call the shots instead.

The hot springs of Yellowstone National Park may be extreme environments, but they are host to a diversity of microbes that could shed light on the evolution of life on Earth and, perhaps, what lurks on distant planets.

Breaks in DNA can wreak havoc in the body, giving rise to cancer and other health problems. Yet sometimes cells rupture their own DNA for a good reason.

How some industrial pollutants or abnormal levels of cellular metabolites contribute to diverse human diseases is now more clearly understood, based on a new study from the University of Wisconsin Carbone Cancer Center (UWCCC) ...

Cocaine, nicotine, capsaicin. These are just three familiar examples of the hundreds of thousands of small molecules (also called specialized or secondary metabolites) that plants use as chemical ammunition to protect themselves ...

A Florida Museum of Natural History study provides new insights into the complex, shared history between blood-sucking lice and the vitamin-producing bacterial sidekicks that enable them to parasitize mammals, including primates ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read the original:
Researchers locate control center for DNA breaks during cell division - Phys.Org