(ORDO NEWS) — Our DNA is tightly packed in the nucleus. Each chromosome is one long DNA molecule wrapped around proteins called histones like a very small thread on a very small spool.
But spermatozoa challenge even chromosome packing skills.
“If DNA under normal conditions took up as much space as a watermelon, then sperm cells would be the size of a tennis ball,” says development researcher at the University Hospital Bonn, Hubert Schorle.
In humans and mice, two proteins called protamines replace histones to pack DNA even tighter, using every bit of space like blocks in a game of Tetris. This process is called hypercondensation.
How this happens is fairly well known, but Schorle and a team of researchers have gone even deeper into the process of hypercondensation and looked at what happens if one of these protamines, PRM2, is disrupted.
During the entire process of creating sperm, a portion of the PRM2 protein called the N-terminus is cut off. This cutting, or splitting, seems to be crucial for the spermatozoa to be… spermatozoa.
“Thus, proper PRM2 cleavage appears to be critical for successful reproduction, however, the function of the PRM2 cleaved domain and PRM2 processing is unknown to date,” the authors write in their paper.
To find out what was going on, the researchers created mutant mice that did not have the PRM2 N-terminus to remove. By closely examining their sperm, the team found that PRM2 definitely needed to be downsized, as mice with uncleaved PRM2 had completely degraded DNA.
“Removal of transition proteins during hypercondensation is impaired,” says first author Lena Arevalo, also from the University Hospital Bonn.
“In addition, condensation occurs too quickly, which leads to breakage of DNA strands.”
This, unsurprisingly, resulted in male infertility, but only in cases where both copies (or alleles) of PRM2 were lost or damaged. When only one of these genes was lost, the mice remained fertile. Below you can see a diagram of this process.
Although we do not yet have direct evidence of this action in humans, it is possible that human fertility problems can sometimes be caused by problems with PRM2 cleavage. A group of researchers is currently investigating whether this is the case.
“There are only a few research groups that are looking at the role of protamines in hypercondensation,” Schorle says.
“To date, we are the only laboratory in the world that has succeeded in creating and breeding PRM1 and PRM2 deficient mice, which are now being used to study the role of these proteins in spermatogenesis.”
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