Abortion, Down syndrome, and infertility are all linked to this hidden DNA process

“If this happens, you will end up with the wrong number of chromosomes in eggs or sperm,” said Neil Hunter, a professor in the Department of Microbiology and Molecular Genetics at the University of California, Davis. “This can lead to infertility, miscarriage, or the birth of children with genetic diseases.”

In a paper published on September 24 in the magazine natureThe Hunter team reports a large new discovery about a process that helps protect these errors. He collected dance design for proteins that link chromosome pairs – to ensure them properly sorted with the development of egg cells and sperm.

Hunter’s discoveries require ways to see molecular events to re -install chromosome with unprecedented details. This included genetic engineering in emerging yeast – a model that has been used for decades to discover the extent of the work of basic cellular processes.

“The chromosome structures that we studied did not change much through development,” Hunter said. “Every protein we looked at in yeast has a direct counterpart in humans.” Its results can improve our understanding of fertility problems and how they are diagnosed and treated in humans.

The formation of chromosome transitions for strong communications

Humans have 46 chromosomes in each of our cells, consisting of 23 pairs of “symmetrical” chromosomes, with one of each pair of each parent. Early of the process of making sperm or eggs, these chromosome pairs are lined up, the chromosomes are broken and joined each other. These chromosome exchanges, called “transitions”, serve two important functions.

First, it helps in ensuring that all chromosome is transferred to the offspring contains a unique mixture of genes from both parents. The transitions also keep chromosomes connected to matching pairs. These connections are directed to distribute chromosomes when cells are divided into the production of eggs and sperm. Hunter said that maintaining intersection communications is crucial in females.

As the chromosomes are approaching the development of egg cells or sperm, matching DNA threads are exchanged and mixed at a short distance to form a structure called “double Holidown intersection”. Then the DNA strands of this structure are cut to join the chromosomes that make up an intersection.

In males, the development of immature sperm cells and then divided immediately and distributing chromosomes to sperm. On the other hand, the egg cells that develop in the ovary of the fetus arrest their development after the transitions were formed. The immature egg cells can remain in the animation suspended for decades after birth, until they are activated to undergo ovulation.

Only then the process returns to the movement: the egg cell is finally divided, and the chromosome pairs that were connected to the transitions are separated to deliver one group of chromosomes to ripe eggs. “Keeping the intersection communications over many years is a major challenge to immature egg cells,” Hunter said.

If the chromosome pairs are not connected by at least one intersection, they can lose their connection with each other, such as two people separated in a similar crowd. This leads to their separation incorrectly when the cell finally is divided, resulting in egg cells with additional or missing chromosomes. This can cause infertility, miscarriage, or genetic conditions such as Down syndrome, where the child is born with an additional copy of chromosome 21, which leads to poor perception, heart defects, hearing loss and other problems.

From yeast to humans

Hunter spent years trying to understand how transitions form and how this process could fail and cause reproductive problems. By studying this process in yeast, researchers can visualize molecular events directly due to the accuracy of the double infection intersection in simultaneous cell groups.

Researchers have identified dozens of proteins that connect and treat these connections. Hunter and his colleague at the time used the Bosetta Changing (Assistant Professor of Biochemistry and Molecular Genetics at the University of Virginia) a technique called “actual time genetics” to investigate the function of these proteins. With this method, they made the cells deteriorate one or more specific proteins within the structures associated with the connection. They can then analyze the DNA from these cells, to see if the connections have been resolved and whether they constitute transmission processes. In this way, they built an image in which a network of proteins work together to ensure the formation of transitions.

“This strategy allowed us to answer a question that was not previously possible,” Hunter said.

They have identified the main proteins such as cohesion that prevents an enzyme called the STR complex (or a blaming complex in humans) from inappropriately dismantling the links before they can form transitions.

“They are protecting the double Holiday intersection,” Hunter said. “This is a major discovery.”

This continuous research project in yeast is widely related to human reproduction because the process has changed very little during development. Failure to protect the intersections of double additions may be associated with fertility problems in humans.

In addition to Tang, postponed doctorate, seven university students at the College of Biological Sciences at the University of California, Davis contributed to this work, including Jennifer Ko, Mohamed Boubhisynzadeh, Emerad Naguin, Natalie Leo, Christopher Ma, Hanio Le Lee.

Among the additional authors on the paper Sarah Hariri, Regeina Bon and John E McCarthy, all members of Hunter Laboratory.

Hunter’s research is funded by the National Health Institutes and Howard Hughes Medical Institute. His work also received funding from the comprehensive UC Davis Cancer Center, the American Cancer Society, the Cancer Research Research Foundation, and the Damon Runyon Cancer Foundation.

Hunter’s research on intersection and repharging is used as advanced scientific facilities in the primary protein facility for the university, the microbiology of MCB light, the genome center, the mouse biology program, and the comprehensive cancer center.