An important new clue for preventing and treating gliomas has been identified in research published in the journal Science, providing a rare window into the biological changes behind glioma development.
In animal models, a team of researchers from Mayo Clinic and Mount Sinai Hospital found that those with a change in DNA known as germline alteration rs55705857 developed gliomas much more frequently and twice as fast compared to animal models without the alteration. In addition to brain tumours, the findings are relevant to other cancers and diseases.
“While we understand much of the biologic function of germline alterations within genes that code for proteins, we know very little about the biologic function of germline alterations outside of genes that code for proteins. In some way, these germline alterations interact with other mutations in cells to accelerate tumour formation,” said co-lead author Robert Jenkins, MD, PhD. “Based on this new understanding of its mechanism of action, future research may lead to novel and specific therapies that target the rs55705857 alteration.”
The study offers new knowledge that may help clinicians determine, pre-surgery, whether a patient has a glioma.
“We expected that rs55705857 would accelerate low-grade glioma development, but we were surprised by the magnitude of that acceleration,” said co-lead author Daniel Schramek, PhD.
There are many alterations, likely thousands, outside of genes associated with the development of cancer and other diseases, but the mechanism of action is only understood for very few, Dr Schramek said.
This study demonstrates that, with the tools of modern molecular/cell biology, it is possible to decipher much of the mechanism of action of such alterations.
There is an elaborate interplay between genes, sex, the environment during growth, and age and how they influence variation in longevity, according to a study published in the journal Science. These findings are an important step in understanding why some people live longer than others and provide a basis for future studies to improve a healthy lifespan.
Robert Williams, PhD, at the University of Tennessee Health Science Center (UTHSC), along with Johan Auwerx, MD, PhD, at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, began a program in 2016 to define genetic factors involved in agieng and lifespan. “Finding common molecular pathways that control differences in rate of aging is critical to our understanding of how individuals differ in their health and lifespan,” Dr Williams said. “Such insights may help us work out ways to intervene rationally.”
Drs Williams and Auwerx received DNA of over 12 000 mice from the National Institute of Aging. Each of the 27 574 genetically heterogeneous mice studied is a full sibling, sharing half its genetic inheritance with each other mouse in the programme, and each has a known lifespan, making them an ideal system to study.
The research team analysed the genes of over 3 000 mice, all of them genetic brothers or sisters which were allowed to live until their natural death. Comparing their DNA to lifespan, the researchers defined stretches of DNA in genomes that affect longevity. The results show the DNA segments, or loci, associated with longevity are largely sex-specific, with females having a region in chromosome 3 that affects lifespan. When the males who died early due to non-aging-related reasons were removed from the analysis, additional genetic signals started to emerge, suggesting some genetic variations only affect lifespan after a certain age.
In addition to finding genetic determinants of longevity, the researchers explored other contributors. In general, bigger mice die younger. The researchers found that some, but not all, of the genetic effects on longevity are through effects on growth. One of the non-genetic effects may be how early access to food affects growth. They observed that mice from smaller litters tended to be heavier adults and live shorter lives. Mice from larger litters that had to share their mother’s milk with more siblings, grew more slowly and lived longer on average. The researchers corroborated these trends of early growth versus longevity in large human datasets with hundreds of thousands of participants.
Beyond characterising how longevity is affected, the researchers worked to find genes most likely to play a role in longevity determination. They measured the effect of DNA variation on how genes are expressed and compared their analyses with multiple human and non-human databases. From this they nominated a few genes likely to modulate aging rates. They then tested the effects of manipulating these genes in roundworms and found that a subset of gene perturbations did in fact affect the lifespan. The results of this study will be a rich resource of aging genes that will hopefully guide the design of therapies that not only extend lifespan, but also healthspan.
Mucus is ubiquitous in nature, from saliva to slugs, and serves many useful functions such as protection of tissues and lubrication. A new study published in Science Advances reveals just how these gooey substances evolved in nature, and how they easily evolve from genes that code for normal proteins.
Comparing mucin genes in 49 mammal species, scientists identified 15 instances in which new mucins appear to have evolved through an additive process that transformed a non-mucin protein into a mucin.
The scientists propose that each of these “mucinisation” events began with a non-mucin protein. At some point, evolution tacked a new section onto this non-mucin base: one consisting of a short chain of amino acids that are decorated with sugar molecules. Over time, this new region got duplicated, with multiple copies added on to elongate the protein even further, making it a mucin.
The doubled regions, called “repeats,” are key to a mucin’s function, say University at Buffalo researchers.
The sugars coating these sections protrude outward like the bristles of a bottle brush, granting mucins the slimy property key to many important tasks that these proteins carry out.
“I don’t think it was previously known that protein function can evolve this way, from a protein gaining repeated sequences. A protein that isn’t a mucin becomes a mucin just by gaining repeats. This is an important way that evolution makes slime. It’s an evolutionary trick, and we now document this happening over and over again,” said Omer Gokcumen, PhD, associate professor of biological sciences.
“The repeats we see in mucins are called ‘PTS repeats’ for their high content of the amino acids proline, threonine and serine, and they aid mucins in their important biological functions that range from lubricating and protecting tissue surfaces to helping make our food slippery so that we can swallow it,” said Stefan Ruhl, DDS, PhD, interim dean of the UB School of Dental Medicine and professor of oral biology. “Beneficial microbes have evolved to live on mucus-coated surfaces, while mucus can at the same time also act as a protective barrier and defend against disease by shielding us from unwanted pathogenic intruders.”
“Not many people know that the first mucin which had been purified and biochemically characterised came from a salivary gland,” Prof Ruhl added. “My lab has been studying mucins in saliva for the last 30 years, mostly because they protect teeth from decay and because they help balance the microbiota in the oral cavity.”
While studying saliva, the team noticed that a small salivary mucin in humans called MUC7 was not present in mice, but they had a similarly sized salivary mucin called MUC10.
It turned out the two mucins were not evolutionarily related. But what the research uncovered next was a surprise. While MUC10 did not appear to be related to MUC7, a protein found in human tears called PROL1 did share a portion of MUC10’s structure. PROL1 looked a lot like MUC10, minus the sugar-coated bottlebrush repeats that make MUC10 a mucin.
“We think that somehow that tear gene ends up repurposed,” Assoc Prof Gokcumen said. “It gains the repeats that give it the mucin function, and it’s now abundantly expressed in mouse and rat saliva.”
The scientists wondered whether other mucins might have formed the same way. They began to investigate and discovered multiple examples of the same phenomena. Though many mucins share common ancestry among various groups of mammals, the team documented 15 instances in which evolution appeared to have converted non-mucin proteins into mucins via the addition of PTS repeats.
And this was “with a pretty conservative look,” Assoc Prof Gokcumen said, noting that the study focused on one region of the genome in a few dozen mammal species. Slime is an “amazing life trait,” he said, curious whether the same evolutionary mechanism might have driven the formation of some mucins in slugs, slime eels and other critters. More research is needed to find an answer.
“How new gene functions evolve is still a question we are asking today,” said Petar Pajic, a UB PhD student in biological sciences and the study’s first author. “Thus, we are adding to this discourse by providing evidence of a new mechanism, where gaining repeated sequences within a gene births a novel function.”
“I think this could have even broader implications, both in understanding adaptive evolution and in possibly explaining certain disease-causing variants,” Pajic added. “If these mucins keep evolving from non-mucins over and over again in different species at different times, it suggests that there is some sort of adaptive pressure that makes it beneficial. And then, at the other end of the spectrum, maybe if this mechanism goes ‘off the rails’ – happening too much, or in the wrong tissue – then maybe it can lead to disease like certain cancers or mucosal illnesses.”
Although low physical activity and greater time spent sitting are well known to be linked to a higher risk of death, a study published in Journal of Aging and Physical Activity showed that a genetic predisposition to longevity was not a substitute for sitting less and greater physical activity, which can benefit even those not gifted with such genes.
“The goal of this research was to understand whether associations between physical activity and sedentary time with death varied based on different levels of genetic predisposition for longevity,” said doctoral student Alexander Posis, lead author of the study.
In 2012, as part of the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health study (OPACH), researchers began measuring the physical activity of 5446 women aged 63 and older, following them through 2020 to determine mortality. Participants wore a research-grade accelerometer for up to seven days to measure how much time they spent moving, the intensity of physical activity, and sedentary time.
Higher levels of light physical activity and moderate-to-vigorous physical activity were found to be associated with lower risk of death. Higher sedentary time was associated with higher risk of mortality. These associations were consistent among women who had different levels of genetic predisposition for longevity.
“Our study showed that, even if you aren’t likely to live long based on your genes, you can still extend your lifespan by engaging in positive lifestyle behaviours such as regular exercise and sitting less,” said Assistant Professor Aladdin H. Shadyab, PhD, senior author. “Conversely, even if your genes predispose you to a long life, remaining physically active is still important to achieve longevity.”
Given the ageing adult population in the United States, and longer time spent engaging in lower intensity activities, the study findings support recommendations that older women should participate in physical activity of any intensity to reduce the risk of disease and premature death, wrote the authors.
University of College London researchers have used gene therapy to partially restore the function of cone receptors in two children with achromatopsia, a rare genetic disorder which can cause partial or complete colourblindness.
The findings, published in Brain, suggest that treatment activates previously dormant communication links between the retina and the brain, thanks to the developing adolescent brain’s plastic nature.
The academically-led study has been running alongside a phase 1/2 clinical trial in children with achromatopsia, using a new way to test whether the treatment is changing the neural pathways specific to the cones.
Achromatopsia is caused by disease-causing variants to one of a few genes. As it affect the cones in the retina, are responsible for colour vision, people with achromatopsia are completely colourblind, while they also have very poor vision and photophobia. Their cone cells do not send signals to the brain, but many remain present, so researchers have been seeking to activate the dormant cells.
Lead author Dr Tessa Dekker said: “Our study is the first to directly confirm widespread speculation that gene therapy offered to children and adolescents can successfully activate the dormant cone photoreceptor pathways and evoke visual signals never previously experienced by these patients.
“We are demonstrating the potential of leveraging the plasticity of our brains, which may be particularly able to adapt to treatment effects when people are young.”
The study involved four young people with achromatopsia aged 10 to 15 years old.
The two trials, which each target a different gene implicated in achromatopsia, are testing gene therapies with the primary aim of establishing that the treatment is safe, while also testing for improved vision. Their results have not yet been fully compiled so the overall effectiveness of the treatments remains to be determined.
The accompanying academic study used a novel functional magnetic resonance imaging (fMRI) mapping approach to separate emerging post-treatment cone signals from existing rod-driven signals in patients, allowing the researchers to pinpoint any changes in visual function, after treatment, directly to the targeted cone photoreceptor system. They employed a ‘silent substitution’ technique using pairs of lights to selectively stimulate cones or rods. The researchers also had to adapt their methods to accommodate eye movements due to nystagmus, another symptom of achromatopsia. The results were compared to tests involving nine untreated patients and 28 volunteers with normal vision.
Each of the four children was treated with gene therapy in one eye, enabling doctors to compare the treatment’s effectiveness with the untreated eye.
For two of the four children, there was strong evidence for cone-mediated signals in the brain’s visual cortex coming from the treated eye, six to 14 months after treatment. Before the treatment, the patients showed no evidence of cone function on any tests. After treatment, their measures closely resembled those from normal sighted study participants.
The study participants also completed a test to distinguish between different levels of contrast. This showed there was a difference in cone-supported vision in the treated eyes in the same two children.
The researchers say they cannot confirm whether the treatment was ineffective in the other two study participants, or if there may have been treatment effects that were not picked up by the tests they used, or if effects are delayed.
Co-lead author Dr Michel Michaelides (UCL Institute of Ophthalmology and Moorfields Eye Hospital), who is also co-investigator on both clinical trials, said: “In our trials, we are testing whether providing gene therapy early in life may be most effective while the neural circuits are still developing. Our findings demonstrate unprecedented neural plasticity, offering hope that treatments could enable visual functions using signalling pathways that have been dormant for years.
“We are still analysing the results from our two clinical trials, to see whether this gene therapy can effectively improve everyday vision for people with achromatopsia. We hope that with positive results, and with further clinical trials, we could greatly improve the sight of people with inherited retinal diseases.”
Dr Dekker added: “We believe that incorporating these new tests into future clinical trials could accelerate the testing of ocular gene therapies for a range of conditions, by offering unparalleled sensitivity to treatment effects on neural processing, while also providing new and detailed insight into when and why these therapies work best.”
One of the study participants commented: “Seeing changes to my vision has been very exciting, so I’m keen to see if there are any more changes and where this treatment as a whole might lead in the future.
“It’s actually quite difficult to imagine what or just how many impacts a big improvement in my vision could have, since I’ve grown up with and become accustomed to low vision, and have adapted and overcome challenges (with a lot of support from those around me) throughout my life.”
A new study published in Nature Genetics has revealed 60 genes linked to autism spectrum disorder (ASD) that may provide important clues to the causes of autism across the full spectrum of the disorder. Five of these genes are heritable instead of new mutated versions, helping explain why autism appears to run in some families.
“Overall, the genes we found may represent a different class of genes that are more directly associated with the core symptoms of ASD than previously discovered genes,” said Professor Wendy Chung, MD, PhD.
Previously, several genes have been linked to autism and as a group are responsible for about 20% of all cases. Most individuals who carry these genes have profound forms of autism and additional neurological issues, such as epilepsy and intellectual disability.
To uncover hidden autism genes that can explain the majority of cases, the researchers tapped into data from nearly 43 000 people with autism.
Five of the genes identified by the new study have a more moderate impact on autism characteristics, including cognition, than previously discovered genes.
“We need to do more detailed studies including more individuals who carry these genes to understand how each gene contributes to the features of autism, but we think these genes will help us unravel the biological underpinnings that lead to most cases of autism,” Prof Chung said.
The five newly identified genes also explain why autism often seems to run in families. Unlike previously known autism genes, which are due to de novo mutations, genetic variants in the five new genes were often inherited from the participant’s parents.
Prof Chung said that many more moderate-effect genes are yet to be discovered, which would help researchers better understand the biology of the brain and behaviour across the full spectrum of autism.
New research suggests that epigenetic information, which turns DNA sections on or off, and is normally reset between generations, is more frequently carried from mother to offspring than previously thought. The findings were published in Nature Communications.
Despite not directly altering the DNA sequence, epigenetic mechanisms can regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal superstructure in which DNA is packaged.
These epigenetic changes can be induced through various such as diet and stress. While epigenetic modifications are reversible, it was thought that they rarely remain through generations in humans despite persisting through multiple cycles of cell replication.
Epigenetic changes can be influenced by environmental variations such as our diet, but these changes do not alter DNA and are normally not passed from parent to offspring.
The new research reveals that the supply of a specific protein in the mother’s egg can affect the genes that drive skeletal patterning of offspring.
Chief investigator Professor Marnie Blewitt said the findings initially left the team surprised.
“It took us a while to process because our discovery was unexpected,” Professor Blewitt said.
“Knowing that epigenetic information from the mother can have effects with life-long consequences for body patterning is exciting, as it suggests this is happening far more than we ever thought.
“It could open a Pandora’s box as to what other epigenetic information is being inherited.”
The research examined the protein SMCHD1, an epigenetic regulator discovered by Prof Blewitt in 2008, and Hox genes, which control the identity of each vertebra during embryonic development in mammals. The epigenetic regulator prevents these genes from being activated too soon.
In this study, the researchers discovered that the amount of SMCHD1 in the mother’s egg affects the activity of Hox genes and influences the patterning of the embryo. Without maternal SMCHD1 in the egg, offspring were born with altered skeletal structures.
First author and PhD researcher Natalia Benetti said this was clear evidence that epigenetic information had been inherited from the mother, rather than just DNA.
“While we have more than 20 000 genes in our genome, only that rare subset of about 150 imprinted genes and very few others have been shown to carry epigenetic information from one generation to another,” Benetti said.
“Knowing this is also happening to a set of essential genes that have been evolutionarily conserved from flies through to humans is fascinating.”
The research showed that SMCHD1 in the egg, which only persists for two days after conception, has a life-long impact.
SMCHD1 variants are linked to developmental disorder Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy (FSHD), a form of muscular dystrophy. The researchers say their findings could have implications for women with SMCHD1 variants and their children in the future.
Research is underway on using on SMCHD1 to design novel therapies to treat developmental disorders, such as Prader Willi Syndrome and the degenerative disorder FSHD.
Genetic mutations behind a genetic kidney disease affecting children and young adults have been fixed in patient-derived kidney cells with a high-capacity DNA ‘repair kit’. The advance, developed by University of Bristol scientists, is published in Nucleic Acids Research.
In this new study, the international team describe how they created a DNA repair vehicle to genetically fix faulty podocin, a common genetic cause of inheritable Steroid Resistant Nephrotic Syndrome (SRNS).
Podocin is a protein normally located on the surface of specialised kidney cells and is essential for kidney function. Faulty podocin, however, remains stuck inside the cell and never makes it to the surface, terminally damaging the podocytes. Since the disease cannot be cured with medications, gene therapy which repairs the genetic mutations causing the faulty podocin offers hope for patients.
Typically, human viruses have been utilised in gene therapy applications to carry out genetic repairs. These are used as a ‘Trojan Horse’ to enter cells carrying the errors. Currently dominating systems include lentivirus (LV), adenovirus (AV) and adeno-associated virus (AAV), which are all relatively harmless viruses that readily infect humans. Their viral shells however restrict the amount of cargo they can carry and deliver, namely the DNA kit necessary for efficient genetic repair. This limits the scope of their application in gene therapy.
By applying synthetic biology techniques, the team led by Dr Francesco Aulicino and Professor Imre Berger, re-engineered baculovirus, a insect virus which has a nearly unlimited cargo capacity.
“What sets apart baculovirus from LV, AV, and AAV is the lack of a rigid shell encapsulating the cargo space.” said Dr Francesco Aulicino, who led the study. The shell of baculovirus resembles a hollow stick, simply lengthening when the cargo increases. This allows a much more sophisticated tool-kit can be delivered by the baculovirus.
First, baculovirus had to be equipped to penetrate human cells which it normally would not do. “We decorated the baculovirus with proteins that enabled it to enter human cells very efficiently.” explained Dr Aulicino. The scientists then used their engineered baculovirus to deliver much larger DNA pieces than was previously possible, and build these into the genomes of a whole range of human cells.
The DNA in the human genome comprises 3 billion base-pairs making up ~25,000 genes, which encode for the proteins that are essential for cellular functions. If faulty base-pairs occur in our genes, faulty proteins are made which can make us ill, resulting in hereditary disease. Gene therapy promises repair of hereditary disease at its very root, by rectifying such errors in our genomes. Gene editing approaches, in particular CRISPR/Cas-based methods, have greatly advanced the field by enabling genetic repair with base-pair precision.
The team used patient-derived podocytes carrying the disease-causing error in the genome to demonstrate the aptitude of their technology. By creating a DNA repair kit, comprising protein-based scissors and the nucleic acid molecules that guide them – and the DNA sequences to replace the faulty gene, the team delivered with a single engineered baculovirus a healthy copy of the podocin gene concomitant with the CRISPR/Cas machinery to insert it with base-pair precision into the genome. This was able to reverse the disease-causing phenotype and restore podocin to the cell surface.
Professor Imre Berger explained: “We had previously used baculovirus to infect cultured insect cells to produce recombinant proteins for studying their structure and function.” This method, called MultiBac, has been highly successful to make very large multiprotein complexes with many subunits, in laboratories world-wide. “MultiBac already exploited the flexibility of the baculovirus shell to deliver large pieces of DNA into the cultured insect cells, instructing them to assemble the proteins we were interested in.” When the scientists realised that the same property could potentially transform gene therapy in human cells, they created this new DNA repair kit.
Dr Aulicino added: “There are many avenues to utilise our system. In addition to podocin repair, we could show that we can simultaneously correct many errors in very different places in the genome efficiently, by using our single baculovirus delivery system and the most recent editing techniques available.”
A new study published in Nature Biotechnology identifies risks in the use of CRISPR gene editing, which is employed in a number of therapies. Looking at its use in T cells, the researchers detected a loss of genetic material in a significant percentage – up to 10% of the treated cells. They explain that such loss can lead to destabilisation of the genome, which might cause cancer.
The study was led by Drs Adi Barzel, Dr Asaf Madi and Dr Uri Ben-David at Tel Aviv University.
Developed about a decade ago, CRISPR cleaves DNA sequences at certain locations in order to delete unwanted segments, or alternately repair or insert beneficial segments. It has already proved impressively effective in treating a range of diseases – cancer, liver diseases, genetic syndromes, and more. In 2020 at the University of Pennsylvania, the first approved clinical trial ever to use CRISPR took T cells from a donor, and expressed an engineered receptor targeting cancer cells, while using CRISPR to destroy genes coding for the original receptor – which otherwise might have caused the T cells to attack cells in the recipient’s body.
In the present study, the researchers sought to examine whether the potential benefits of CRISPR therapeutics might be offset by risks resulting from the cleavage itself, assuming that broken DNA is not always able to recover.
Dr Ben-David and his research associate Eli Reuveni explained: “The genome in our cells often breaks due to natural causes, but usually it is able to repair itself, with no harm done. Still, sometimes a certain chromosome is unable to bounce back, and large sections, or even the entire chromosome, are lost. Such chromosomal disruptions can destabilise the genome, and we often see this in cancer cells. Thus, CRISPR therapeutics, in which DNA is cleaved intentionally as a means for treating cancer, might, in extreme scenarios, actually promote malignancies.”
To examine the extent of potential damage, the researchers repeated the 2020 Pennsylvania experiment, cleaving the T cells’ genome in exactly the same locations – chromosomes 2, 7, and 14. Using single-cell RNA sequencing, they analysed each cell separately and measured the expression levels of each chromosome in every cell.
They detected a significant loss of genetic material in some of the cells. For example, when chromosome 14 had been cleaved, about 5% of the cells showed little or no expression of this chromosome. When all chromosomes were cleaved simultaneously, the damage increased, with 9%, 10%, and 3% of the cells unable to repair the break in chromosomes 14, 7, and 2 respectively. The three chromosomes did differ, however, in the extent of the damage they sustained.
Dr Madi and his student Ella Goldschmidt explained: “Single-cell RNA sequencing and computational analyses enabled us to obtain very precise results. We found that the cause for the difference in damage was the exact place of the cleaving on each of the three chromosomes. Altogether, our findings indicate that over 9% of the T-cells genetically edited with the CRISPR technique had lost a significant amount of genetic material. Such loss can lead to destabilisation of the genome, which might promote cancer.”
Based on their findings, the researchers caution that extra care should be taken when using CRISPR therapeutics. They also propose alternative, less risky, methods, for specific medical procedures, and recommend further research into two kinds of potential solutions: reducing the production of damaged cells or identifying damaged cells and removing them before the material is administered to the patient.
Dr Barzel and his PhD student Alessio Nahmad conclude: “Our intention in this study was to shed light on potential risks in the use of CRISPR therapeutics,” adding that as scientists, they “examine all aspects of an issue, both positive and negative, and look for answers.”
During sperm production, an enormous amount of DNA has to be packed into a very small space without breaking anything. Protamines are the key to this compression, wrapping the DNA thread tightly, but humans have a second type of protamine which had an unknown purpose. Insights into this key mechanism are described in PLoS Genetics.
During the production of human sperm cells, DNA has to be packed into a tiny space, not unlike trying to cram too many clothes into a tiny suitcase to go on holiday. DNA is normally in a comparatively loose tangle. In sperm cells, however, it is enormously compressed. The 23 DNA threads have a total length of one metre and have to be packed into a head just three thousandths of a millimetre in diameter. All of this must happen without the delicate DNA threads tearing or becoming inextricably tangled up.
We often sit on packed suitcases to close them, and the body uses a similar trick during spermatogenesis. “If DNA were to take up as much space as a watermelon under normal circumstances, sperm cells would then only be as big as a tennis ball,” explained Professor Hubert Schorle from the University Hospital Bonn.
This process is termed hypercondensation. In their loose state, DNA threads are wrapped around numerous spherical protein molecules, the histones. In this state, they resemble 23 tiny strings of pearls. During hypercondensation, the histones are first exchanged for transition proteins, which are in turn are replaced by so-called protamines. Due to their chemical composition, protamines exert a very strong attraction on DNA, causing it to wrap itself in very firm and tightly loops around the protamine
“Most mammals seem to produce only one type of protamine, PRM1,” explained 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.” Until now, it was unclear what this second protamine is needed for. It was however known that some parts of it are successively cut off during sperm development.
These cut-off parts that appear to be immensely important, according to the new study. When mice produce only a truncated PRM2 molecule that lacks the cut-off snippets, they are infertile. “The removal of transition proteins during hypercondensation is impaired,” Dr Arévalo said. “In addition, the condensation seems to proceed too quickly, causing the DNA strands to break.”
It is possible that a defective protamine 2 can also lead to infertility in human males. The team now plans to investigate this hypothesis further, thanks to their lab being the only one so far that has successfully generated and bred PRM and PRM2 deficient mouse lines.
