DNA damaged induced cell death in oocytes

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 crosso
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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Metadaten
Author:Jakob Gebel, Marcel Tuppi, Nicole Sänger, Björn Schumacher, Volker Dötsch
URN:urn:nbn:de:hebis:30:3-574196
DOI:http://dx.doi.org/10.3390/molecules25235714
ISSN:1420-3049
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=33287328
Parent Title (German):Molecules
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2020/12/03
Date of first Publication:2020/12/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/01/10
Tag:CEP-1; development; oocyte death ; p53 family; p63; p73; quality control; tetramerization; transcriptional activity
Volume:25
Issue:23, Article 5714
Pagenumber:24
Institutes:Biochemie und Chemie
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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