Nature: Damage to the father's DNA from radiation is passed on to offspring

Does the radiation to fathers affect their children? This is one of
the most persistent problems in radiation biology.
Using Caenorhabditis elegans as a model, Professor Björn Schumacher and his team found that damage to mature sperm caused by radiation cannot be repaired, but is passed on to offspring
.
In contrast, female eggs either repair the damage accurately or, if the damage is too severe, are eliminated with no damage transfer
.
However, when an egg is fertilized with a sperm damaged by radiation, the maternal repair protein provided by the egg attempts to repair the paternal DNA
.
To do this, the body uses a very error-prone repair mechanism and randomly fuses broken DNA fragments
.
The random fusion of these breaks leads to structural changes
in paternal chromosomes.
The resulting offspring now carry chromosomal damage, which in turn exhibits severe developmental defects
.
This study lays the foundation for a better understanding of the
genetic effect mechanisms of paternal radiation exposure.

The work is now published in the journal Nature as "Inheritance of paternal DNA damage by histone-mediated repair restriction
.
"

Offspring from exposed male nematodes and healthy female nematodes carry so-called structural variations—random connections
of chromosomal parts.
In offspring, these distortions lead to repeated fractures, but this damage can no longer be repaired
.
Instead, damaged chromosomes are protected by proteins that densely wrap long strands of DNA (i.
e.
, histones) and cannot be repaired
accurately.
In densely packed DNA, repair proteins can no longer reach breaks
.
The filled DNA structure is tightly linked by specific histones HIS-24 and HPL-1
.
When these histones are removed, paternally inherited damage is completely eliminated, allowing for surviving offspring
.
Histones control the accessibility of DNA repair, and this discovery provides an effective therapeutic target for the treatment of
radiation damage.

Is this also related to the harm of radiation to the human body? In addition to the study of nematodes, the team also found the same structural variation, known as randomly combined chromosomes
, in humans.
Also here, chromosomal aberrations are inherited by the father and not by the mother
.
To do this, the scientists analyzed various datasets from the 1,000 Genome Project, including genetic data from more than 1,000 people, as well as genetic data
from their respective mothers, fathers, and children.

"Genomic aberrations, particularly structural variations in chromosomes, are thought to increase the risk of
diseases such as autism and schizophrenia.
" This also means that in humans, mature sperm need special protection from radiation damage, and damaged mature sperm should not be used for conception
.
"This damage can be caused during radiotherapy or chemotherapy, so it poses a risk
within a two-month period of producing new sperm to replace the damaged sperm.
" This is because newly produced sperm have the ability to repair damage accurately compared to
mature sperm.

Interestingly, scientists have also found structural variations
in chromosomes in nematodes in both wild and humans.
These results suggest that damage to mature sperm and inaccurate repair of paternal DNA in fertilized eggs may be major drivers of genetic diversity during evolution and may be responsible for
genetic diseases in humans.

The study was carried out at the Institute for Gemoric and Disease Genomic Stability in the CECAD Cluster of Excellence in Aging Research at the University of Cologne and was funded by the German Research Foundation (DFG
).