Sea urchin embryo as a model for analysis of the signaling pathways linking DNA damage checkpoint, DNA repair and apoptosis

Abstract

DNA integrity checkpoint control was studied in the sea urchin early embryo. Treatment of the embryos with genotoxic agents such as methyl methanesulfonate (MMS) or bleomycin induced the activation of a cell cycle checkpoint as evidenced by the occurrence of a delay or an arrest in the division of the embryos and an inhibition of CDK1/cyclin B activating dephosphorylation. The genotoxic treatment was shown to induce DNA damage that depended on the genotoxic concentration and was correlated with the observed cell cycle delay. At low genotoxic concentrations, embryos were able to repair the DNA damage and recover from checkpoint arrest, whereas at high doses they underwent morphological and biochemical changes characteristic of apoptosis. Finally, extracts prepared from embryos were found to be capable of supporting DNA repair in vitro upon incubation with oligonucleotides mimicking damage. Taken together, our results demonstrate that sea urchin early embryos contain fully functional and activatable DNA damage checkpoints. Sea urchin embryos are discussed as a promising model to study the signaling pathways of cell cycle checkpoint, DNA repair and apoptosis, which upon deregulation play a significant role in the origin of cancer.

The Influence of Bioactive Oxylipins from Marine Diatoms on Invertebrate Reproduction and Development

“…DNA repair would normally occur during the G phases, therefore cellular surveillance would not operate until numerous cycles of DNA replication and mitotic cleavage had occurred, with or without genetic damage. There is some suggestion that this generalisation may not hold entirely true for sea urchins [155,156], however most sources are in support of the critical stage of the mid-blastula transition [157,158] which leaves a considerable portion of early embryogenesis without an apparent mechanism for genetic surveillance. Le Bouffant et al .…”

Overview of the molecular defense systems used by sea urchin embryos to cope with UV radiation

“…Although UVC (<280 nm) has no environmental relevance, (it is absorbed by ozone and does not reach the Earth), the study provided many information on the profiles of induced DNA-repair genes in exposed embryos: i) ercc1, involved in NER; ii) xrcc4, xrcc5 and xrcc6 involved in NHEJ (Non-homologous endjoining); iii) pcna involved both in NER and BER (Reinardy and Bodnar, 2015), see Table 3. BER and NHEJ DNA repair activities have been measured in vitro using embryonic extracts, and they appeared functional in embryos where DNA damage had been induced by MMS, a DNA alkylating agent (Le Bouffant et al, 2007). In addition, the study showed that early embryos could activate DNA damage checkpoint pathways, i.e.…”

“…In addition, the study showed that early embryos could activate DNA damage checkpoint pathways, i.e. a cell cycle delay and no activation of the complex CDK1/cyclin B (Le Bouffant et al, 2007), that would explain the cleavage delay observed in early stage embryos after irradiation. As a further step, if the amount of DNA lesions were to exceed the efficiency of the repair systems, the unrepaired photoproducts could trigger apoptosis in sea urchin embryos, as reported for mammalian cells (Batista et al, 2009).…”

Apoptosis: focus on sea urchin development

“…Then sea urchin embryos was discussed as a promising model for the study of the signalling pathways of cell cycle checkpoint, DNA repair and apoptosis, which upon deregulation play a significant role in the origin of cancer [59].…”