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

Cell repair machinery is responsible for protecting the genome from endogenous and exogenous effects that induce DNA damage. Mutations that occur in somatic cells lead to dysfunction in certain tissues or organs, while a violation of genomic integrity during the embryonic period often leads to death. A mammalian embryo’s ability to respond to damaged DNA and repair it, as well as its sensitivity to specific lesions, is still not well understood. In this review, we combine disparate data on repair processes in the early stages of preimplantation development in mammalian embryos.

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The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

Cancers ◽

10.3390/cancers13030479 ◽

2021 ◽

Vol 13 (3) ◽

pp. 479

Author(s):

Pavel Vodicka ◽

Ladislav Andera ◽

Alena Opattova ◽

Ludmila Vodickova

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Dna Repair ◽

Dna Lesions ◽

Cell Cycle Checkpoint ◽

Solid Cancer ◽

Genomic Integrity ◽

Repair Capacity ◽

Mutational Status ◽

Telomere Homeostasis

The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capacity, and telomere shortening constitute the hallmarks of malignant diseases. DNA damage response (DDR) is a signaling network to process DNA damage with importance for both cancer development and chemotherapy outcome. DDR represents the complex events that detect DNA lesions and activate signaling networks (cell cycle checkpoint induction, DNA repair, and induction of cell death). TP53, the guardian of the genome, governs the cell response, resulting in cell cycle arrest, DNA damage repair, apoptosis, and senescence. The mutational status of TP53 has an impact on DDR, and somatic mutations in this gene represent one of the critical events in human carcinogenesis. Telomere dysfunction in cells that lack p53-mediated surveillance of genomic integrity along with the involvement of DNA repair in telomeric DNA regions leads to genomic instability. While the role of individual players (DDR, telomere homeostasis, and TP53) in human cancers has attracted attention for some time, there is insufficient understanding of the interactions between these pathways. Since solid cancer is a complex and multifactorial disease with considerable inter- and intra-tumor heterogeneity, we mainly dedicated this review to the interactions of DNA repair, telomere homeostasis, and TP53 mutational status, in relation to (a) cancer risk, (b) cancer progression, and (c) cancer therapy.

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DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization

eLife ◽

10.7554/elife.04883 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 45

Author(s):

Stephanie J Papp ◽

Anne-Laure Huber ◽

Sabine D Jordan ◽

Anna Kriebs ◽

Madelena Nguyen ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Circadian Clock ◽

Transcriptional Response ◽

Genotoxic Stress ◽

Genomic Integrity ◽

Clock Time ◽

Dna Repair Enzymes ◽

Repair Enzymes ◽

Specific Protease

The circadian transcriptional repressors cryptochrome 1 (Cry1) and 2 (Cry2) evolved from photolyases, bacterial light-activated DNA repair enzymes. In this study, we report that while they have lost DNA repair activity, Cry1/2 adapted to protect genomic integrity by responding to DNA damage through posttranslational modification and coordinating the downstream transcriptional response. We demonstrate that genotoxic stress stimulates Cry1 phosphorylation and its deubiquitination by Herpes virus associated ubiquitin-specific protease (Hausp, a.k.a Usp7), stabilizing Cry1 and shifting circadian clock time. DNA damage also increases Cry2 interaction with Fbxl3, destabilizing Cry2. Thus, genotoxic stress increases the Cry1/Cry2 ratio, suggesting distinct functions for Cry1 and Cry2 following DNA damage. Indeed, the transcriptional response to genotoxic stress is enhanced in Cry1−/− and blunted in Cry2−/− cells. Furthermore, Cry2−/− cells accumulate damaged DNA. These results suggest that Cry1 and Cry2, which evolved from DNA repair enzymes, protect genomic integrity via coordinated transcriptional regulation.

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Mechanisms of Genome Maintenance in Plants: Playing It Safe With Breaks and Bumps

Frontiers in Genetics ◽

10.3389/fgene.2021.675686 ◽

2021 ◽

Vol 12 ◽

Author(s):

Aamir Raina ◽

Parmeshwar K. Sahu ◽

Rafiul Amin Laskar ◽

Nitika Rajora ◽

Richa Sao ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Plant Growth ◽

Genomic Instability ◽

Model Organisms ◽

Ultraviolet Rays ◽

Genomic Integrity ◽

Wide Range ◽

Repair Pathways ◽

Living Organisms

Maintenance of genomic integrity is critical for the perpetuation of all forms of life including humans. Living organisms are constantly exposed to stress from internal metabolic processes and external environmental sources causing damage to the DNA, thereby promoting genomic instability. To counter the deleterious effects of genomic instability, organisms have evolved general and specific DNA damage repair (DDR) pathways that act either independently or mutually to repair the DNA damage. The mechanisms by which various DNA repair pathways are activated have been fairly investigated in model organisms including bacteria, fungi, and mammals; however, very little is known regarding how plants sense and repair DNA damage. Plants being sessile are innately exposed to a wide range of DNA-damaging agents both from biotic and abiotic sources such as ultraviolet rays or metabolic by-products. To escape their harmful effects, plants also harbor highly conserved DDR pathways that share several components with the DDR machinery of other organisms. Maintenance of genomic integrity is key for plant survival due to lack of reserve germline as the derivation of the new plant occurs from the meristem. Untowardly, the accumulation of mutations in the meristem will result in a wide range of genetic abnormalities in new plants affecting plant growth development and crop yield. In this review, we will discuss various DNA repair pathways in plants and describe how the deficiency of each repair pathway affects plant growth and development.

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Early mammalian development: from basic research to the clinic

The International Journal of Developmental Biology ◽

10.1387/ijdb.180409as ◽

2019 ◽

Vol 63 (3-4-5) ◽

pp. 73-75 ◽

Cited By ~ 1

Author(s):

Aneta Suwi&nacute;ska ◽

Anna Ajduk

Keyword(s):

Embryonic Development ◽

Basic Research ◽

Embryonic Cell ◽

Mammalian Development ◽

Cell Lineages ◽

Mammalian Embryos ◽

New Ideas ◽

Totipotent Cell ◽

Early Mammalian Development ◽

Mammalian Embryonic Development

Preimplantation embryonic development lays the foundations for the future individual. Fertilization, cleavage, differentiation of the first embryonic cell lineages and implantation of the embryo into the maternal uterus are absolutely critical for proper embryogenesis. Solving unanswered questions as well as creating new ideas and theories constitute the main axis of the basic research, which is driven by the curiosity of scientists and their desire to explore the unknown. We researchers have been exploring the development of mammalian embryos for decades, searching for the answer to the most fundamental question in the whole area of biology: how a complex organism derives from a single totipotent cell, a zygote. Due to obvious ethical concerns, animals, such as mice and, currently more and more often, cattle, pigs and rabbits, have become useful models for studying human embryonic development. Unprecedented advancement in cell and molecular biology techniques witnessed in the last years allows us to deepen our understanding of mammalian embryonic development.

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Archaeal DNA Repair Mechanisms

Biomolecules ◽

10.3390/biom10111472 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1472

Author(s):

Craig J. Marshall ◽

Thomas J. Santangelo

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Molecular Mechanisms ◽

Genomic Integrity ◽

Dna Stability ◽

Dna Repair Mechanisms ◽

Environmental Extremes ◽

Repair Mechanisms ◽

Repair Pathways ◽

Damage Types

Archaea often thrive in environmental extremes, enduring levels of heat, pressure, salinity, pH, and radiation that prove intolerable to most life. Many environmental extremes raise the propensity for DNA damaging events and thus, impact DNA stability, placing greater reliance on molecular mechanisms that recognize DNA damage and initiate accurate repair. Archaea can presumably prosper in harsh and DNA-damaging environments in part due to robust DNA repair pathways but surprisingly, no DNA repair pathways unique to Archaea have been described. Here, we review the most recent advances in our understanding of archaeal DNA repair. We summarize DNA damage types and their consequences, their recognition by host enzymes, and how the collective activities of many DNA repair pathways maintain archaeal genomic integrity.

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Long-term efficacy of a new medical device containing Fernblock® and DNA repair enzyme complex in the treatment and prevention of cancerization field in patients with actinic keratosis.

Journal of Current Medical Research and Opinion ◽

10.15520/jcmro.v2i02.129 ◽

2019 ◽

Vol 2 (02) ◽

pp. 80-89

Author(s):

Blanca De Unamuno Bustos ◽

Natalia Chaparr´´o Aguilera ◽

Inmaculada Azorín García ◽

Anaid Calle Andrino ◽

Margarita Llavador Ros ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Medical Device ◽

Actinic Keratosis ◽

Statistical Significance ◽

Dna Lesions ◽

Enzyme Complex ◽

Repair Enzyme ◽

P53 Expression ◽

Cancerization Field

Actinic keratosis (AKs) are part of the cancerization field, a region adjacent to AKs containing subclinical and histologically abnormal epidermal tissue due to Ultraviolet (UV)-induced DNA damage. The photoproducts as consequence of DNA damage induced by UV are mainly cyclobutane pyrimidine dimers (CPDs). Fernblock® demonstrated in previous studies significant reduction of the number of CPDs induced by UV radiation. Photolyases are a specific group of enzymes that remove the major UV-induced DNA lesions by a mechanism called photo-reactivation. A monocentric, prospective, controlled, and double blind interventional study was performed to evaluate the effect of a new medical device (NMD) containing a DNA-repair enzyme complex (photolyases, endonucleases and glycosilases), a combination of UV-filters, and Fernblock® in the treatment of the cancerization field in 30 AK patients after photodynamic therapy. Patients were randomized into two groups: patients receiving a standard sunscreen (SS) andpatients receiving the NMD. Clinical, dermoscopic, reflectance confocal microscopy (RCM) and histological evaluations were performed. An increase of AKs was noted in all groups after three months of PDT without significant differences between them (p=0.476). A significant increase in the number of AKs was observed in SS group after six (p=0.026) and twelve months of PDT (p=0.038); however, this increase did not reach statistical significance in the NMD group. Regarding RCM evaluation, honeycomb pattern assessment after twelve months of PDT showed significant differences in the extension and grade of the atypia in the NMD group compared to SS group (p=0.030 and p=0.026, respectively). Concerning histopathological evaluation, keratinocyte atypia grade improved from baseline to six months after PDT in all the groups, with no statistically significant differences between the groups. Twelve months after PDT, p53 expression was significantly lower in the NMD group compared to SS group (p=0.028). The product was well-tolerated, with no serious adverse events reported. Our results provide evidence of the utility of this NMD in the improvement of the cancerization field and in the prevention of the development of new AKs.

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Virtual ultrasound embryo autopsy – myth or reality? Part 1

10.21516/2413-1458-2017-16-3-257-264 ◽

2017 ◽

Author(s):

A.Yu. Blinov

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Prenatal Diagnosis ◽

Medical Imaging ◽

Embryonic Development ◽

Human Embryos ◽

Review Of Literature ◽

Embryonic Period ◽

New Methods ◽

Central Nervous System Defects

A review of literature data on the study of human embryos using new methods of medical imaging is given. The possibility of prenatal diagnosis of severe central nervous system defects has been demonstrated already in the embryonic period at 8–10 weeks of gestation or at the age of 16 to 23 stages of the embryonic development period

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PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome

Nature Communications ◽

10.1038/s41467-019-13641-0 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Deepti Sharma ◽

Louis De Falco ◽

Sivaraman Padavattan ◽

Chang Rao ◽

Susana Geifman-Shochat ◽

...

Keyword(s):

Dna Damage ◽

Mutational Analysis ◽

Catalytic Efficiency ◽

Double Strand Breaks ◽

Genomic Integrity ◽

Dna Double Strand Breaks ◽

Strand Breaks ◽

Nucleosome Core ◽

Epigenetic Marker ◽

Kinetics Of

AbstractThe poly(ADP-ribose) polymerase, PARP1, plays a key role in maintaining genomic integrity by detecting DNA damage and mediating repair. γH2A.X is the primary histone marker for DNA double-strand breaks and PARP1 localizes to H2A.X-enriched chromatin damage sites, but the basis for this association is not clear. We characterize the kinetics of PARP1 binding to a variety of nucleosomes harbouring DNA double-strand breaks, which reveal that PARP1 associates faster with (γ)H2A.X- versus H2A-nucleosomes, resulting in a higher affinity for the former, which is maximal for γH2A.X-nucleosome that is also the activator eliciting the greatest poly-ADP-ribosylation catalytic efficiency. The enhanced activities with γH2A.X-nucleosome coincide with increased accessibility of the DNA termini resulting from the H2A.X-Ser139 phosphorylation. Indeed, H2A- and (γ)H2A.X-nucleosomes have distinct stability characteristics, which are rationalized by mutational analysis and (γ)H2A.X-nucleosome core crystal structures. This suggests that the γH2A.X epigenetic marker directly facilitates DNA repair by stabilizing PARP1 association and promoting catalysis.

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