Study sheds light on process that plays central role

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During sperm production, a huge amount of DNA has to be packed into a very small space without breaking anything. A central role is played by certain proteins around which the DNA thread is wound: protamines. A recent study from the University of Bonn provides new insights into this important mechanism. The results were published in the journal PLoS genetics.

If you’re complaining again that your suitcase is far too small as your vacation approaches, you should look to human sperm for inspiration. During their production, they are faced with an almost insoluble task. They have to pack 23 DNA strands with a total length of one meter into a head with a diameter of only three thousandths of a millimeter. And in doing so, the delicate threads should not get tangled in an inextricable knot, nor tear.

We often sit on the suitcase to close it. The body uses a similar trick during spermatogenesis. Normally, DNA forms a relatively loose tangle. In sperm, however, it is extremely compressed. “If DNA took up as much space as a watermelon under normal circumstances, then sperm would be as big as a tennis ball,” says Professor Hubert Schorle from the Institute of Pathology at Bonn University Hospital. .

DNA must be enormously compressed

Biologists call this process hypercondensation. In their loose state, the DNA threads are wrapped around numerous spherical protein molecules, the histones. In this state, they look like 23 small pearl necklaces. During hypercondensation, histones are first exchanged for transition proteins. In a later step, these are replaced by so-called protamines. Due to their chemical composition, protamines exert a very strong attraction on DNA. The wire therefore wraps in very firm and tight loops around the protamine

“Most mammals seem to produce only one type of protamine, PRM1,” says Dr. Lena Arévalo, a postdoctoral researcher in Schorle’s group. “In humans, but also rodents like mice, it’s different – they have a second type, PRM2.” The exact reason why this second protamine is needed was not known until now. However, it was known that some parts of it are successively cut off during sperm development.

And it is precisely these cut parts that seem extremely important, according to the new study. When mice produce only a truncated PRM2 molecule lacking the clipping extracts, they are infertile. “The elimination of transition proteins during hypercondensation is impaired,” explains Arévalo. “Furthermore, the condensation appears to be happening too quickly, causing DNA strands to break.”

The hope of therapies against male infertility

It is possible that defective protamine 2 could also cause infertility in males of our own species. The team now plans to investigate this hypothesis further. “There are only a few research groups that analyze the role of protamines in hypercondensation,” says Schorle, who is also a member of the transdisciplinary research area (TRA) “Life and Health” at the University of Bonn. “We are to date the only laboratory in the world to have succeeded in generating and selecting lines of mice deficient in PRM1 and PRM2 which are now used to study the role of these proteins in spermatogenesis.” In the medium term, this could also lead to new therapies against male infertility, hopes the researcher.

Funding

The study was supported by the German Research Foundation (DFG) and the FEMHABIL program at the University Hospital Bonn.

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Material provided by University of Bonn. Note: Content may be edited for style and length.

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