DNA Damaged Induced Cell Death in Oocytes

Gebel, Jakob; Tuppi, Marcel; Sänger, Nicole; Schumacher, Björn; Dötsch, Volker

doi:10.3390/molecules25235714

Cited by 33 publications

(32 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In short, the TA variant of P63 and P73 share the highest degree of sequence homology to P53 and have similar functions (depending on the isoform), including the transactivation of multiple P53 targets such as MDM2 (which in turn also negatively regulates P63 and P73), P21, PUMA, NOXA, and Bax, thus also playing a role in cell cycle arrest, DNA repair, and apoptosis [107,109,110,[112][113][114][115][122][123][124][125]. For example, TAp763 and TAp63 have been implicated in DNA-damage induced apoptosis in oocytes, suggesting a role in maintaining the genomic integrity of the female germline [113,[126][127][128]. Similarly, a more recently identified new P63 isoform, GTAp63, was found to be highly expressed in male germ cells, which induce apoptosis (including the transactivation of PUMA and NOXA) after cisplatin-induced DNA damage [106].…”

Section: Box 2 Background Information Of the P53 Homologs P63 And P73mentioning

confidence: 99%

Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells—Relevance for Understanding (Germ Cell) Tumorigenesis

Timmerman

Remmers

Hillenius

et al. 2021

IJMS

View full text Add to dashboard Cite

The P53 pathway is the most important cellular pathway to maintain genomic and cellular integrity, both in embryonic and non-embryonic cells. Stress signals induce its activation, initiating autophagy or cell cycle arrest to enable DNA repair. The persistence of these signals causes either senescence or apoptosis. Over 50% of all solid tumors harbor mutations in TP53 that inactivate the pathway. The remaining cancers are suggested to harbor mutations in genes that regulate the P53 pathway such as its inhibitors Mouse Double Minute 2 and 4 (MDM2 and MDM4, respectively). Many reviews have already been dedicated to P53, MDM2, and MDM4, while this review additionally focuses on the other factors that can deregulate P53 signaling. We discuss that P14ARF (ARF) functions as a negative regulator of MDM2, explaining the frequent loss of ARF detected in cancers. The long non-coding RNA Antisense Non-coding RNA in the INK4 Locus (ANRIL) is encoded on the same locus as ARF, inhibiting ARF expression, thus contributing to the process of tumorigenesis. Mutations in tripartite motif (TRIM) proteins deregulate P53 signaling through their ubiquitin ligase activity. Several microRNAs (miRNAs) inactivate the P53 pathway through inhibition of translation. CCCTC-binding factor (CTCF) maintains an open chromatin structure at the TP53 locus, explaining its inactivation of CTCF during tumorigenesis. P21, a downstream effector of P53, has been found to be deregulated in different tumor types. This review provides a comprehensive overview of these factors that are known to deregulate the P53 pathway in both somatic and embryonic cells, as well as their malignant counterparts (i.e., somatic and germ cell tumors). It provides insights into which aspects still need to be unraveled to grasp their contribution to tumorigenesis, putatively leading to novel targets for effective cancer therapies.

show abstract

Section: Box 2 Background Information Of the P53 Homologs P63 And P73mentioning

confidence: 99%

Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells—Relevance for Understanding (Germ Cell) Tumorigenesis

Timmerman

Remmers

Hillenius

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…They depend on a G2/M DDR and P63, a member of the P53 family, activated by ATM and CHK1. During their meiotic arrest, DNA-damaged oocytes undergo a specific P63-dependent apoptotic death [79] only for severe DNA damage [80]. Later, in metaphase I and II oocytes of growing follicles, the DNA damage-induced arrest is overridden by the spindle assembly checkpoint (SAC) [81,82].…”

Section: Cell Death and P53 Signalingmentioning

confidence: 99%

Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies

Molinaro

Martoriati

Cailliau

2021

Cancers

View full text Add to dashboard Cite

Cells respond to genotoxic stress through a series of complex protein pathways called DNA damage response (DDR). These monitoring mechanisms ensure the maintenance and the transfer of a correct genome to daughter cells through a selection of DNA repair, cell cycle regulation, and programmed cell death processes. Canonical or non-canonical DDRs are highly organized and controlled to play crucial roles in genome stability and diversity. When altered or mutated, the proteins in these complex networks lead to many diseases that share common features, and to tumor formation. In recent years, technological advances have made it possible to benefit from the principles and mechanisms of DDR to target and eliminate cancer cells. These new types of treatments are adapted to the different types of tumor sensitivity and could benefit from a combination of therapies to ensure maximal efficiency.

show abstract

“…During meiotic prophase one, DNA is intentionally “damaged” so that recombination can occur. Mechanisms are in place to repair this damage but if the DNA is not repaired a DNA damage response is triggered leading to the elimination of defective oocytes (for review see Gebel et al, 2020 ). The ATM kinase is upregulated in damaged oocytes leading to activation of CHK2 ( Hirao et al, 2002 ).…”

Section: Elimination Of Oocytes With Defective Dna Repair or Synapsismentioning

confidence: 99%

Regulation of Meiotic Prophase One in Mammalian Oocytes

Wang

Pepling

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

In female mammals, meiotic prophase one begins during fetal development. Oocytes transition through the prophase one substages consisting of leptotene, zygotene, and pachytene, and are finally arrested at the diplotene substage, for months in mice and years in humans. After puberty, luteinizing hormone induces ovulation and meiotic resumption in a cohort of oocytes, driving the progression from meiotic prophase one to metaphase two. If fertilization occurs, the oocyte completes meiosis two followed by fusion with the sperm nucleus and preparation for zygotic divisions; otherwise, it is passed into the uterus and degenerates. Specifically in the mouse, oocytes enter meiosis at 13.5 days post coitum. As meiotic prophase one proceeds, chromosomes find their homologous partner, synapse, exchange genetic material between homologs and then begin to separate, remaining connected at recombination sites. At postnatal day 5, most of the oocytes have reached the late diplotene (or dictyate) substage of prophase one where they remain arrested until ovulation. This review focuses on events and mechanisms controlling the progression through meiotic prophase one, which include recombination, synapsis and control by signaling pathways. These events are prerequisites for proper chromosome segregation in meiotic divisions; and if they go awry, chromosomes mis-segregate resulting in aneuploidy. Therefore, elucidating the mechanisms regulating meiotic progression is important to provide a foundation for developing improved treatments of female infertility.

show abstract

DNA Damaged Induced Cell Death in Oocytes

Cited by 33 publications

References 160 publications

Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells—Relevance for Understanding (Germ Cell) Tumorigenesis

Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells—Relevance for Understanding (Germ Cell) Tumorigenesis

Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies

Regulation of Meiotic Prophase One in Mammalian Oocytes

Contact Info

Product

Resources

About