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The arrest of ooctyes at the four genome copy stage appears to provide the informational redundancy needed to repair damage in the DNA of the germline. [26] The repair process used likely involves homologous recombinational repair. [26] [27] [28] Prophase arrested oocytes have a high capability for efficient repair of DNA damages. [27]
In mammalian females the period of arrest may last for years. During this period of arrest, oocytes are subject to spontaneous DNA damage including double-strand breaks. However, the oocytes can efficiently repair DNA double-strand breaks, allowing the restoration of genetic integrity and the protection of offspring health. [8]
Oocyte abnormalities can be caused by a variety of genetic factors affecting different stages in meiosis. [1] Moreover, ageing is associated with oocyte abnormalities since higher maternal age is associated with oocytes with a reduced gene expression of spindle assembly checkpoints which are important in maintaining stability in the genome.
In mouse oocytes, DNA damage induces meiotic prophase I arrest that is mediated by the spindle assembly checkpoint. [57] Arrested oocytes do not enter the subsequent stage, anaphase I. DNA double strand breaks, UVB and ionizing radiation induced DNA damage cause an effective block to anaphase promoting complex activity. [57]
The response of oocytes to DNA double-strand break damage involves a pathway hierarchy in which ATR kinase signals to CHEK2 which then activates p53 and p63 proteins. [ 15 ] In the fruit fly Drosophila , irradiation of germ line cells generates double-strand breaks that result in cell cycle arrest and apoptosis .
DNA damage-induced oocyte apoptosis depends on the efficiency of the DNA repair machinery that in turn declines with age. Survival of oocytes following chemotherapy or aging can be enhanced by increased expression of Rad51. [35]
The response of oocytes to DNA double-strand break damage involves a pathway hierarchy in which ATR kinase signals to CHEK2 which then activates p53 and p63 proteins. [ 15 ] In the fruitfly Drosophila , irradiation of germ line cells generates double-strand breaks that result in cell cycle arrest and apoptosis .
The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis. [19] In the yeast Saccharomyces cerevisiae, SMC6 is necessary for resistance to DNA damage as well as for damage-induced interchromosomal and sister chromatid recombination. [20]