Regulation and coordination of the different DNA damage responses in Drosophila

Baonza, Antonio; Tur-Gracia, Sara; Pérez-Aguilera, Marina; Estella, Carlos

doi:10.3389/fcell.2022.993257

Cited by 15 publications

(19 citation statements)

References 122 publications

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“…Because CifAB-expressing CI males suffer from depleted lncRNA and enhanced DNA damage, resulting in sperm development with altered H-P abundance, we next investigated whether fertilization by the compromised CI sperm causes adverse effects in embryos during nuclear divisions. Previous studies showed that Drosophila embryonic DNA damage is only evident in late stages of development ~6 hours after egg deposition (AED) toward gastrulation (33)(34)(35), as the cells at this stage become hyperprolifertive, and hence, more susceptible to damage (36)(37)(38). Although CI is often associated with a first-mitotic division defect within 1 hour of egg fertilization, additional developmental defects also occur in late CI embryos developing through the preblastoderm divisions, syncytial, and cellularized blastoderms (10,(39)(40)(41).…”

Section: Embryos Succumb To Dna Damagementioning

confidence: 99%

Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality

Kaur,

McGarry,

Shropshire

et al. 2024

Science

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The extent to which prophage proteins interact with eukaryotic macromolecules is largely unknown. In this work, we show that cytoplasmic incompatibility factor A (CifA) and B (CifB) proteins, encoded by prophage WO of the endosymbiont Wolbachia, alter long noncoding RNA (lncRNA) and DNA during Drosophila sperm development to establish a paternal-effect embryonic lethality known as cytoplasmic incompatibility (CI). CifA is a ribonuclease (RNase) that depletes a spermatocyte lncRNA important for the histone-to-protamine transition of spermiogenesis. Both CifA and CifB are deoxyribonucleases (DNases) that elevate DNA damage in late spermiogenesis. lncRNA knockdown enhances CI, and mutagenesis links lncRNA depletion and subsequent sperm chromatin integrity changes to embryonic DNA damage and CI. Hence, prophage proteins interact with eukaryotic macromolecules during gametogenesis to create a symbiosis that is fundamental to insect evolution and vector control.

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Section: Embryos Succumb To Dna Damagementioning

confidence: 99%

Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality

Kaur,

McGarry,

Shropshire

et al. 2024

Science

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“…This complex pathway allows cells to detect genomic damage and to mount an appropriate cellular response, from pausing the cell cycle and repairing DNA damage, to entering senescence, to undergoing apoptosis [1,2]. However, while many of the molecular components of the DDR are highly conserved across eukaryotic evolution, there is profound variation in how different cells respond to DNA damage based on such factors as signaling pathway status, tissue context, cell cycling status, development stage, and more [3][4][5][6][7][8][9][10]. Facing the same type and amount of DNA damage, cells in different contexts can vary widely in their propensity to undergo apoptosis in the face of DNA damage.…”

Section: Introductionmentioning

confidence: 99%

Wnt signaling modulates the response to DNA damage in theDrosophilawing imaginal disc by regulating the EGFR pathway

Ewen-Campen,

Perrimon

2024

Preprint

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Despite the deep conservation of the DNA damage response pathway (DDR), cells in different contexts vary widely in their susceptibility to DNA damage and their propensity to undergo apoptosis as a result of genomic lesions. One of the cell signaling pathways implicated in modulating the DDR is the highly conserved Wnt pathway, which is known to promote resistance to DNA damage caused by ionizing radiation in a variety of human cancers. However, the mechanisms linking Wnt signal transduction to the DDR remain unclear. Here, we use a genetically encoded system in Drosophila to reliably induce consistent levels of DNA damage in vivo, and demonstrate that canonical Wnt signaling in the wing imaginal disc buffers cells against apoptosis in the face of DNA double-strand breaks. We show that Wg, the primary Wnt ligand in Drosophila, activates Epidermal Growth Factor Receptor (EGFR) signaling via the ligand-processing protease Rhomboid, which in turn modulates the DDR in a Chk2, p53, and E2F1-dependent manner. These studies provide mechanistic insight into the modulation of the DDR by the Wnt and EGFR pathways in vivo in a highly proliferative tissue. Furthermore, they reveal how the growth and patterning functions of Wnt signaling are coupled with pro-survival, anti-apoptotic activities, thereby facilitating developmental robustness in the face of genomic damage.

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“…Moreover, the knowledge is accumulated that apoptosis is also induced by DNA damage [ 15 , 16 ]. Recently, Baonza et al reviewed about the genetic regulation leading to either apoptosis or non-apoptosis corresponding to the DNA damage induced by ionizing radiation in Drosophila [ 17 ]. However, to the best of our knowledge, no reports have comprehensively explored the direct relationship between apoptosis and somatic cell mutations induced by DNA damage.…”

Section: Introductionmentioning

confidence: 99%

“…1 . Moreover, it is well known that DNA repair system plays important roles in mutagenic process [ 1 ] and also apoptotic process is regulated by DNA repair [ 16 , 17 ]. Therefore, we examined how the DNA repair pathway influences apoptosis and mutation, and how apoptosis affects the behavior of mutated cells.…”

Section: Introductionmentioning

confidence: 99%

Mutation and apoptosis are well-coordinated for protecting against DNA damage-inducing toxicity in Drosophila

et al. 2023

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Background Apoptotic cell death is an important survival system for multicellular organisms because it removes damaged cells. Mutation is also a survival method for dealing with damaged cells in multicellular and also unicellular organisms, when DNA lesions are not removed. However, to the best of our knowledge, no reports have comprehensively explored the direct relationship between apoptosis and somatic cell mutations induced by various mutagenic factors. Results Mutation was examined by the wing-spot test, which is used to detect somatic cell mutations, including chromosomal recombination. Apoptosis was observed in the wing discs by acridine orange staining in situ. After treatment with chemical mutagens, ultraviolet light (UV), and X-ray, both the apoptotic frequency and mutagenic activity increased in a dose-dependent manner at non-toxic doses. When we used DNA repair-deficient Drosophila strains, the correlation coefficient of the relationship between apoptosis and mutagenicity, differed from that of the wild-type. To explore how apoptosis affects the behavior of mutated cells, we determined the spot size, i.e., the number of mutated cells in a spot. In parallel with an increase in apoptosis, the spot size increased with MNU or X-ray treatment dose-dependently; however, this increase was not seen with UV irradiation. In addition, BrdU incorporation, an indicator of cell proliferation, in the wing discs was suppressed at 6 h, with peak at 12 h post-treatment with X-ray, and that it started to increase again at 24 h; however, this was not seen with UV irradiation. Conclusion Damage-induced apoptosis and mutation might be coordinated with each other, and the frequency of apoptosis and mutagenicity are balanced depending on the type of DNA damage. From the data of the spot size and BrdU incorporation, it is possible that mutated cells replace apoptotic cells due to their high frequency of cell division, resulting in enlargement of the spot size after MNU or X-ray treatment. We consider that the induction of mutation, apoptosis, and/or cell growth varies in multi-cellular organisms depending on the type of the mutagens, and that their balance and coordination have an important function to counter DNA damage for the survival of the organism.

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Regulation and coordination of the different DNA damage responses in Drosophila

Cited by 15 publications

References 122 publications

Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality

Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality

Wnt signaling modulates the response to DNA damage in theDrosophilawing imaginal disc by regulating the EGFR pathway

Mutation and apoptosis are well-coordinated for protecting against DNA damage-inducing toxicity in Drosophila

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