Speed limit on DNA-making sets pace for life’s first steps — ScienceDaily

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The fruit fly is made by the mother of the scorpion and only teaches part of the genetic building blocks needed for the survival of its offspring. The rest must be produced by the fertilized egg in the first few steps of its growth.

Scientists have been confused for twenty years because of this seemingly unnecessary detention. Now, researchers at Princeton University have shown that the inhibitory mechanism controlled by an enzyme called RNR is actually the key to embryo survival. Too much material in the early days led to the disaster of the life form that had just started.

"This study shows us what fragile development is," said Stanislav Shvartsman, professor of chemical and biological engineering at Princeton University and Lewis-Sigler Institute for Integrative Genomics. "We asked a question, why does the mother have to be so frugal?" This question led Shvartsman to test what happens when the embryo inherited a large number of these building blocks. The answer is not very good. “We realized that without limiting supply, there would be a time conflict that would destroy multiple processes in the embryo,” he said.

In a study reported in the March 14th issue of the journal Current Biology the team followed the embryonic development of two groups of flies: a set of normally supplied DNA building blocks called nucleotides, The other group is about 10 times the amount. The results show that when the embryo has more nucleotides available from the beginning, its DNA replication mechanism works at a very fast rate, and the subsequent process is treated rudely and later causes serious defects.

Nareg Djabrayan is an associate researcher at the Lewis-Sigler Institute of Integrated Genomics at Princeton University and the first author of the paper, comparing the replication process to a machine. "When you provide too much input for that machine, its speed limit is broken," he said. "It's too fast. It mixes with other things that must happen at the same time."

The problems that began in the first critical step were exacerbated in later stages. As the embryo begins to shape, its midline (the spine analog of the fly) is disastrously distorted.

"After that, they will become kaput," Shvartsman said.

It turns out that the quantitative detention of mothers in previous work played an important role in the timing of early life, providing a natural limit to the speed of development. Finally, those fruit flies that start with excess essential ingredients cannot develop into a viable organism.

According to Stefano Di Talia, a cell biologist at Duke University, these findings mark the shift in thinking of researchers who control genomic control from mother to offspring. "This paper is important because it shows that strict control of nucleotide levels is not only energy-efficient, but also essential for normal embryonic development," he said. Di Talia suggests that future research will be based on this work to understand how cell cycle time affects tissue mechanics.

In this case, RNR enzymes – the common goal of anticancer therapy – play a key role in balancing the speed of the most basic processes of cells and cell division. Uncontrolled cell division and growth are hallmarks of cancer. In addition to answering basic questions about the early life of animals, the researchers believe that this work can open up new avenues to study cancer drugs in embryonic development.

In addition to Shvartsman and Djabrayan, the team also includes Celia M. Smits, Matej Krajnc and Tomer Stern from Princeton; Shigehiro Yamada and Christine A. Rushlow from New York University; and William C from the Janelia Research Park at Howard Hughes Medical Institute. Lemon and Philipp J. Keller.

The project was funded by the National Institute of General Medicine of the National Institutes of Health.


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