DNA Damaged Induced Cell Death in Oocytes - Kölner UniversitätsPublikationsServer

Gebel, Jakob, Tuppi, Marcel ORCID: 0000-0002-2963-5902, Saenger, Nicole, Schumacher, Bjoern and Doetsch, Volker (2020). DNA Damaged Induced Cell Death in Oocytes. Molecules, 25 (23). BASEL: MDPI. ISSN 1420-3049

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DOI:10.3390/molecules25235714

Abstract

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.

Item Type:

Journal Article

Creators:

Creators	Email	ORCID	ORCID Put Code
Gebel, Jakob	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Tuppi, Marcel	UNSPECIFIED	orcid.org/0000-0002-2963-5902	UNSPECIFIED
Saenger, Nicole	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Schumacher, Bjoern	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Doetsch, Volker	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED