Oocyte Quality Control: Causes, Mechanisms, and Consequences

p53 gene family members in humans and other organisms encode a large number of protein isoforms whose functions are largely undefined. Using Drosophila as a model, we find that a p53B isoform is expressed predominantly in the germline where it colocalizes with p53A into subnuclear bodies. It is only p53A, however, that mediates the apoptotic response to ionizing radiation in the germline and soma. In contrast, p53A and p53B are both required for the normal repair of meiotic DNA breaks, an activity that is more crucial when meiotic recombination is defective. We find that in oocytes with persistent DNA breaks p53A is also required to activate a meiotic pachytene checkpoint. Our findings indicate that Drosophila p53 isoforms have DNA lesion and cell type-specific functions, with parallels to the functions of mammalian p53 family members in the genotoxic stress response and oocyte quality control.

Download Full-text

CHK2 sets the stage for CK1 in oocyte quality control

Cell Death and Differentiation ◽

10.1038/s41418-018-0107-6 ◽

2018 ◽

Vol 25 (6) ◽

pp. 1007-1009 ◽

Cited By ~ 2

Author(s):

Sebastian Kehrloesser ◽

Marcel Tuppi ◽

Volker Dötsch

Keyword(s):

Quality Control ◽

Oocyte Quality

Download Full-text

Drosophila p53 isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control

10.1101/2020.07.21.214692 ◽

2020 ◽

Author(s):

Ananya Chakravarti ◽

Heshani N. Thirimanne ◽

Brian R. Calvi

Keyword(s):

Quality Control ◽

Family Members ◽

P53 Gene ◽

Genotoxic Stress ◽

Oocyte Quality ◽

Protein Isoforms ◽

Dna Breaks ◽

P53 Family ◽

Dna Lesion ◽

P53 Isoforms

Abstractp53 gene family members in humans and other organisms encode a large number of protein isoforms whose functions are largely undefined. Using Drosophila as a model, we find that a p53B isoform is expressed predominantly in the germline where it colocalizes with p53A into subnuclear bodies. It is only p53A, however, that mediates the apoptotic response to ionizing radiation in the germline and soma. In contrast, p53A and p53B both respond to meiotic DNA breaks and are required during oogenesis to prevent persistent germline DNA breaks, an activity that is more crucial when meiotic recombination is defective. We find that in oocytes with persistent DNA breaks p53A is required to activate a meiotic pachytene checkpoint. Our findings indicate that Drosophila p53 isoforms have DNA lesion and cell type-specific functions, with parallels to the functions of mammalian p53 family members in the genotoxic stress response and oocyte quality control.

Download Full-text

Impeding DNA Break Repair Enables Oocyte Quality Control

10.1101/277913 ◽

2018 ◽

Cited By ~ 1

Author(s):

Huanyu Qiao ◽

H.B.D. Prasada Rao ◽

Yan Yun ◽

Sumit Sandhu ◽

Jared H. Fong ◽

...

Keyword(s):

Quality Control ◽

Oocyte Quality ◽

Double Strand Breaks ◽

Negative Regulator ◽

Dna Double Strand Breaks ◽

Strand Breaks ◽

Homologous Chromosomes ◽

Chromosome Synapsis ◽

Sumo Ligase ◽

Induced Apoptosis

SUMMARYOocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death is triggered by defects in chromosome synapsis and recombination, which involve repair of programmed DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocytes elimination in meiotic mutants require RNF212. RNF212 sensitizes cells to DSB-induced apoptosis within a narrow window when chromosomes desynapse during the transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a “memory” of meiotic defects that enables quality control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.

Download Full-text