DNA Damaged Induced Cell Death in Oocytes.

Tytuł:: DNA Damaged Induced Cell Death in Oocytes.
Autorzy:: Gebel J; Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany.
Tuppi M; Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany.
Sänger N; Department for Gynecological Endocrinology and Reproductive Medicine, University Hospital of Bonn, Venusberg-Campus 1, 53217 Bonn, Germany.
Schumacher B; Institute for Genome Stability in Aging and Disease, Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center, and Center for Molecular Medicine, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Dötsch V; Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany.
Źródło:: Molecules (Basel, Switzerland) [Molecules] 2020 Dec 03; Vol. 25 (23). Date of Electronic Publication: 2020 Dec 03.
Typ publikacji:: Journal Article; Review
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, c1995-
MeSH Terms:: Cell Death/*genetics
DNA Damage/*genetics
Oocytes/*physiology
Animals ; DNA Breaks, Double-Stranded ; DNA Repair/genetics ; Humans
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Grant Information:: DO 545/18-1, SCHU 2494/3-1, SCHU 2494/7-1, SCHU 2494/10-1, SCHU 2494/11-1 Deutsche Forschungsgemeinschaft
Contributed Indexing:: Keywords: CEP-1; development; oocyte death; p53 family; p63; p73; quality control; tetramerization; transcriptional activity
Entry Date(s):: Date Created: 20201208 Date Completed: 20210406 Latest Revision: 20210406
Update Code:: 20240104
PubMed Central ID:: PMC7730327
DOI:: 10.3390/molecules25235714
PMID:: 33287328
: Czasopismo naukowe

Pełny tekst

The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible. Central to this monitoring system that is conserved from nematodes and fruit fly to humans is the p53 protein family, and in vertebrates in particular p63. In mammals, oocytes are stored for a long time in the prophase of meiosis I which, in humans, can last more than 50 years. During the entire time of this arrest phase, the DNA damage checkpoint remains active. The treatment of female cancer patients with DNA damaging irradiation or chemotherapeutics activates this checkpoint and results in elimination of the oocyte pool causing premature menopause and infertility. Here, we review the molecular mechanisms of this quality control system and discuss potential therapeutic intervention for the preservation of the oocyte pool during chemotherapy.

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