Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis
| العنوان: | Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis |
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| المؤلفون: | M. Janaki Ramaiah, Utpal Bhadra, Arpita Sarkar, Manika Pal-Bhadra, S.N.C.V.L. Pushpavalli, Debabani Roy Chowdhury |
| المصدر: | BMC Molecular Biology BMC Molecular Biology, Vol 14, Iss 1, p 1 (2013) |
| بيانات النشر: | BioMed Central, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Genome instability, Male, Cell cycle checkpoint, lcsh:QH426-470, DNA damage, Chk2, Mitosis, Embryonic Development, Protein Serine-Threonine Kinases, Genomic Instability, 03 medical and health sciences, 0302 clinical medicine, Animals, Drosophila Proteins, Syncytial embryos, lcsh:QH573-671, Molecular Biology, Checkpoint Kinase 2, Mitotic catastrophe, 030304 developmental biology, Mof, Histone Acetyltransferases, 0303 health sciences, Anaphase bridges, biology, lcsh:Cytology, fungi, Nuclear Proteins, Cell Cycle Checkpoints, Drosophila melanogaster, Molecular biology, Cell biology, lcsh:Genetics, Histone, biology.protein, Female, 030217 neurology & neurosurgery, Drosophila Protein, Research Article, DNA Damage |
| الوصف: | Background In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Results Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof 1 /+; mnk p6 /+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. Conclusion mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using Drosophila as model system and carry out the interaction of MOF with the known components of the DNA damage pathway. |
| اللغة: | English |
| تدمد: | 1471-2199 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46e902d8bc111485c02198cebf272789Test http://europepmc.org/articles/PMC3566930Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....46e902d8bc111485c02198cebf272789 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712199 |
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