Protein Function Repairing Genetic Damage in Spermatogenesis Discovered

Since the 1990’s scientists have known that ATR is found in spermatocytes but its function was not clear. Later on, it was discovered that the protein might be involved in DNA repair, but again, the process how this happens remained a puzzle for years, until recently.

Now according to the findings, researchers from the Universitat Autònoma de Barcelona, Institute of Biotechnology and Biomedicine (UAB-IBB) have discovered the whole process in the functioning of ATR.

They’ve also uncovered how meiotic recombination occurs during the growth of spermatocytes.

Sperm and Ova Development

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The process that forms sperm or ova is called meiosis, it’s a special type of cell division. Both the sperm and over are called haploid gametes because each contains a single copy of the chromosome (either X or Y).

Now, in the process of meiosis, two rounds of cell divisions take place, which ends up halving the number of chromosomes. When this process is successful, that’s how the correct amount of chromosomes is achieved in the species, after fertilization.

In the first process of division, DNA strands break on purpose, which then undergoes a special repair or what the experts call meiotic recombination. This then induces the exchange of genetic material and information between both and leads to homologous chromosomes.

Ideally, the whole process needs to be seamless that’s why in case an error occurs, it automatically leads to issues in the integrity of the genome. That’s how we end up with a defective sperm or ova.

This is Where the Study Comes In …

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Now, in the study, the experts took mice with deficiencies in their ATR expression and were able to inhibit this protein with drugs. “We have managed to demonstrate that the protein is necessary for ensuring proper completion of the meiotic recombination acting in the early stages in spermatocytes,” explained Ignasi Roig the co-author of the report, which now appears in Nature Communications.

The study was a collaboration between UAB-IBB, CNIO (Spanish National Cancer Research Center,) MSKCC (Memorial Sloan-Kettering Cancer Center) and HHMI (Howard Hughes Medical Institute, New York.

The work proved that ATR is essential in the recruitment of two proteins namely RAD51 and DMC1. Where both of this is needed in the genetic repair process, basically in single-stranded DNA sections. This is created during the processing of DNA double-strand breaks, from the very onset of meiosis.

Reduced Amounts of ATR

Roig pointed out that spermatocytes with lesser amounts of ATR present problems during pairing in homologous chromosomes, when repairing broken DNA strands, and also during the swapping of material between homologous chromosomes that is ideally a must in correct formation of sperm.

When anomalies accumulate, they can trigger a halt in cell progression and eventually programmed cell death which ends up blocking the process of spermatogenesis.

Why the Study Matters

The unmasking of how the ATR does function in meiotic recombination provides a significant opening in the study of mammalian meiosis –taking into account that scholars can finally establish its part in DNA repair, in spermatocytes with the use of genetic and pharmacological tools,” explained Sarai Pacheco, the lead author in the research.

The study also points out to possible unwanted effects of using ATR inhibitor drugs in humans.