The importance of DNA repair for maintaining oocyte quality in response to anti-cancer treatments, environmental toxins and maternal ageing

Winship, Amy; Stringer, Jessica M; Liew, Seng H.; Hutt, Karla J.

doi:10.1093/humupd/dmy002

Cited by 129 publications

(118 citation statements)

References 158 publications

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“…In the present study, we identified two novel heterozygous frameshift mutations of the FANCL gene in POI patients, p.Gln350Valfs*18 and p.Met247Asnfs*4, that resulted in the loss of ubiquitin‐ligase activity and impaired DNA damage repair capacity. It is well documented that the maintenance of genome stability and integrity is a vital determinant of cell viability, and the germ cell genome is especially vulnerable to ubiquitous DNA insults (Winship, Stringer, Liew, & Hutt, 2018). Moreover, increasing evidence suggests that mutations of the genes involved in DNA repair underlie the pathogenesis of POI (Huhtaniemi et al, 2018; Jiao et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

FANCL gene mutations in premature ovarian insufficiency

et al. 2020

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884Update of variants iden fi ed in the pancrea c β-cell K ATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes 983 Fundamental role of BMP15 in human ovarian folliculogenesis revealed by null and missense muta ons associated with primary ovarian insuffi ciency Raff aella Rosse , Ilaria Ferrari , Ilaria Beste , Silvia Moleri , Francesco Branca , Luisa Petrone , Palma Finelli and Luca Persani 998 Func onal characteriza on of the fi rst missense variant in CEP78 , a founder allele associated with cone-rod dystrophy, hearing loss, and reduced male fer lity 1025 Cri cal assessment of secondary fi ndings in genes linked to primary arrhythmia syndromes Volume 41 , Number 5 was mailed the week of April 06, 2020 Front Cover: The cover image is based on the Research Ar cle FANCL gene muta ons in premature ovarian insuffi ciency by Yajuan Yang et al., h ps://doi.

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Section: Discussionmentioning

confidence: 99%

FANCL gene mutations in premature ovarian insufficiency

et al. 2020

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“…DNA breaks are more likely to remain unrepaired in aged oocytes owing to reduced expression of DNA repair genes such as ATM, BRCA1, and RAD51 (Titus et al, 2013;Winship et al, 2018). Consistent with this, oocytes from mice with reduced BRCA1 expression or disrupted RAD51 function exhibit increased DNA damage (Kujjo et al, 2010;Titus et al, 2013;Winship et al, 2018). Thus, low levels of DNA damage may persist throughout oocyte growth without inducing apoptosis, especially when DNA repair capacity is compromised.…”

Section: Introductionmentioning

confidence: 81%

“…In contrast, full activation of TAp63 at high irradiation doses (0.45 Gy) causes virtually all oocytes to succumb (Suh et al, 2006). DNA breaks are more likely to remain unrepaired in aged oocytes owing to reduced expression of DNA repair genes such as ATM, BRCA1, and RAD51 (Titus et al, 2013;Winship et al, 2018). Consistent with this, oocytes from mice with reduced BRCA1 expression or disrupted RAD51 function exhibit increased DNA damage (Kujjo et al, 2010;Titus et al, 2013;Winship et al, 2018).…”

Section: Introductionmentioning

confidence: 87%

Oocytes mount a noncanonical DNA damage response involving APC-Cdh1–mediated proteolysis

Subramanian

Greaney

Wei

et al. 2020

Journal of Cell Biology

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In mitotic cells, DNA damage induces temporary G2 arrest via inhibitory Cdk1 phosphorylation. In contrast, fully grown G2-stage oocytes readily enter M phase immediately following chemical induction of DNA damage in vitro, indicating that the canonical immediate-response G2/M DNA damage response (DDR) may be deficient. Senataxin (Setx) is involved in RNA/DNA processing and maintaining genome integrity. Here we find that mouse oocytes deleted of Setx accumulate DNA damage when exposed to oxidative stress in vitro and during aging in vivo, after which, surprisingly, they undergo G2 arrest. Moreover, fully grown wild-type oocytes undergo G2 arrest after chemotherapy-induced in vitro damage if an overnight delay is imposed following damage induction. Unexpectedly, this slow-evolving DDR is not mediated by inhibitory Cdk1 phosphorylation but by APC-Cdh1–mediated proteolysis of the Cdk1 activator, cyclin B1, secondary to increased Cdc14B-dependent APC-Cdh1 activation and reduced Emi1-dependent inhibition. Thus, oocytes are unable to respond immediately to DNA damage, but instead mount a G2/M DDR that evolves slowly and involves a phosphorylation-independent proteolytic pathway.

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“…Many working in oncofertility research are now turning their attention to the development of drugs that can prevent initial oocyte damage, thus preserving the ovarian follicle pool as well as ovarian endocrine function. Recent evidence suggests that cancer therapies reduce the primordial follicle pool by promoting DNA damage and apoptosis in their oocytes (Winship et al 2018). The proapoptotic protein p53 upregulated modulator of apoptosis (PUMA) was identified as critical apoptotic trigger in ovarian reserve depletion following chemotherapy.…”

Section: Speakers: Iain Clarke Ray Rodgers Graeme Martin Karla Huttmentioning

confidence: 99%

Fifty years of reproductive biology in Australia: highlights from the 50th Annual Meeting of the Society for Reproductive Biology (SRB)

Bromfield

Dowland

Dunleavy

et al. 2019

Reprod. Fertil. Dev.

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The 2018 edition of the Society for Reproductive Biology’s (SRB) Annual Meeting was a celebration of 50 years of Australian research into reproductive biology. The past 50 years has seen many important contributions to this field, and these advances have led to changes in practice and policy, improvements in the efficiency of animal reproduction and improved health outcomes. This conference review delivers a dedicated summary of the symposia, discussing emerging concepts, raising new questions and proposing directions forward. Notably, the symposia discussed in this review emphasised the impact that reproductive research can have on quality of life and the health trajectories of individuals. The breadth of the research discussed encompasses the central regulation of fertility and cyclicity, life course health and how the environment of gametes and embryos can affect subsequent generations, significant advances in our understanding of placental biology and pregnancy disorders and the implications of assisted reproductive technologies on population health. The importance of a reliable food supply and protection of endangered species is also discussed. The research covered at SRB’s 2018 meeting not only recognised the important contributions of its members over the past 50 years, but also highlighted key findings and avenues for innovation moving forward that will enable the SRB to continue making significant contributions for the next 50 years.

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The importance of DNA repair for maintaining oocyte quality in response to anti-cancer treatments, environmental toxins and maternal ageing

Cited by 129 publications

References 158 publications

FANCL gene mutations in premature ovarian insufficiency

FANCL gene mutations in premature ovarian insufficiency

Oocytes mount a noncanonical DNA damage response involving APC-Cdh1–mediated proteolysis

Fifty years of reproductive biology in Australia: highlights from the 50th Annual Meeting of the Society for Reproductive Biology (SRB)

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