Features of DNA Repair in the Early Stages of Mammalian Embryonic Development

Khokhlova, Evgenia V; Fesenko, Zoia; Sopova, Julia V.; Leonova, E. I.

doi:10.3390/genes11101138

Cited by 34 publications

(24 citation statements)

References 65 publications

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“…Spermatozoa possess a truncated BER containing only the first enzyme, the 8-oxoguanine DNA glycosylase, OGG1, to remove oxidized base adducts after oxidative damage (8-Oxoguanine lesions) [55]. Meiotic recombination in oocyte arrested in meiosis I uses HR, while oocytes in meiosis II accumulate transcripts from all the DNA repair pathways to be used after fertilization in the early embryo before transcription starts at the four-cell stage, and the canonical DDR is activated [56,57].…”

Section: Selection Of the Repair Mechanismsmentioning

confidence: 99%

“…Another member of the P53 family is involved in oocytes facing cumulative DNA damage when arrested in the prophase of the first meiosis division for many years in ovaries [77]. Prophase 1 oocytes in primordial follicles are unable to respond immediately to DNA damage, while all components necessary for the DNA repair including direct lesion reversal, NER, BER, MMR, HR, and NHEJ processes are present [56,78]. They depend on a G2/M DDR and P63, a member of the P53 family, activated by ATM and CHK1.…”

Section: Cell Death and P53 Signalingmentioning

confidence: 99%

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

Molinaro

Martoriati

Cailliau

2021

Cancers

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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.

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Section: Selection Of the Repair Mechanismsmentioning

confidence: 99%

Section: Cell Death and P53 Signalingmentioning

confidence: 99%

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

Molinaro

Martoriati

Cailliau

2021

Cancers

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“…Although a remarkable acceleration of 8OHdG repair by the base excision repair pathway has been reported in the mouse oocyte following fertilization, OGG1 expression seems particularly low compared to male germ cells [77]. Therefore, spermatozoa carrying high levels of 8OHdG at the time of fertilization can undergo an incomplete DNA repair in the zygote, and this may impair the preimplantation embryo development [84] and fetal growth [85]. In addition, incomplete repair of sperm 8OHdG lesions has been linked to defects in offspring, including cancer and reduced lifespan [86,87].…”

Section: Origin and Consequences Of Dna Damage In Ejaculated Spermatozoamentioning

confidence: 99%

Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development

et al. 2021

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Reactive oxygen species (ROS) generated at low levels during mitochondrial respiration have key roles in several signaling pathways. Oxidative stress (OS) arises when the generation of ROS exceeds the cell’s antioxidant scavenging ability and leads to cell damage. Physiological ROS production in spermatozoa regulates essential functional characteristics such as motility, capacitation, acrosome reaction, hyperactivation, and sperm-oocyte fusion. OS can have detrimental effects on sperm function through lipid peroxidation, protein damage, and DNA strand breakage, which can eventually affect the fertility of an individual. Substantial evidence in the literature indicates that spermatozoa experiencing OS during in vitro manipulation procedures in human- and animal-assisted reproduction are increasingly associated with iatrogenic ROS production and eventual impairment of sperm function. Although a direct association between sperm OS and human assisted reproductive techniques (ART) outcomes after in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) is still a matter of debate, studies in animal models provide enough evidence on the adverse effects of sperm OS in vitro and defective fertilization and embryo development. This review summarized the literature on sperm OS in vitro, its effects on functional ability and embryo development, and the approaches that have been proposed to reduce iatrogenic sperm damage and altered embryonic development.

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“…All the heterozygous females inherited the CHEK1 R442Q mutation from their father as their mother has two copies of the normal CHEK1 gene. Since the paternal genome starts to express after the major zygotic genome activation during the 4 to 8-cell stage in humans (Kermi et al, 2019; Khokhlova et al, 2020; Xue et al, 2013; Yan et al, 2013), the CHEK1 R442Q protein derived from the mutated paternal copy of CHEK1 will likely be present from the 8-cell stage onwards. Therefore, the small elevation of CHEK1 kinase activity does not appear to arrest cell division after the 8-cell stage in human embryos.…”

Section: Table1mentioning

confidence: 99%

A small increase inCHEK1activity leads to the arrest of the first zygotic division in human

Chen

Guo

Wang

et al. 2020

Preprint

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The first mitotic division in mammalian zygotes is unique. The fertilized egg reactivates its cell cycle, and the maternal and paternal genomes start to reprogram to become totipotent. The first division is very sensitive to a range of perturbations, particularly the DNA damage, leading to the embryo's failure to enter the first mitosis. We discovered that a point mutation in the human CHEK1 gene resulted in an Arginine 442 to Glutamine change at the C-terminus of the CHEK1 protein. CHEK1 R442Q mutation caused the zygote to arrest just before the first division. Heterozygote individuals appeared to be healthy except that the female carriers are infertile. Expressing the corresponding mouse mutant Chk1 protein in zygotes also caused arrest before the first mitosis. Treating Chk1 R442Q mouse zygotes with low concentrations of CHEK1 inhibitor enabled the embryos to overcome the cell cycle arrest and resume normal development. Our results revealed an unexpected zygote mitotic checkpoint, which is extremely sensitive to the CHEK1 kinase activity. The fine-tuning of the DNA damage checkpoint permits the arrested one-cell embryos to overcome the first mitotic block and develop into healthy animals. These findings have important implications in assisted human reproduction.

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Features of DNA Repair in the Early Stages of Mammalian Embryonic Development

Cited by 34 publications

References 65 publications

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

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

Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development

A small increase inCHEK1activity leads to the arrest of the first zygotic division in human

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