Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis

Abstract

BackgroundIn 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.ResultsDrosophila 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 mof1/+; mnkp6/+ 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.Conclusionmof 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.

Broad-Band Activatable White-Opsin

“…By combining all three opsins, the construction of a “white-opsin” with a broad-band activation spectrum that is stimulated by white light should be possible. To test this, MultiSite Gateway® Technology [ 24 ] was used to fuse multiple opsin-encoding genes, ChR2, C1V1 and ReaChR, under the control of a cytomegalovirus (CMV) promoter (Figs 1 and 2 ). A plasmid map of this white-opsin is shown in Fig 1B .…”

CHK2 kinase in the DNA damage response and beyond

“…In D. melanogaster a role for CHK2 at the meiotic checkpoint is controversial ( Abdu et al, 2002 ; Masrouha et al, 2003 ). In the same organism, the absence of CHK2 leads to the accumulation of abnormal nuclei in the syncytial embryo, resulting probably from defects in arresting or eliminating cells with endogenous DNA damage ( Pushpavalli et al, 2013 ). In mice, CHK2 is activated by ATM in female germ cells during early meiosis ( Miles et al, 2010 ) and regulates cell cycle progression and spindle assembly during oocyte maturation and early embryo development ( Dai et al, 2014 ).…”

Transcriptomic analysis of the differentiating ovary of the protogynous ricefield eel Monopterus albus

“…In teleosts such as zebrafish [ 16 ] and tilapia [ 17 ], Aldh1a2 and Cyp26a1 regulate the homeostasis of RA and play critical roles in meiotic initiation. These studies suggest that the metabolism and roles of RA may be conserved in meiosis of teleosts although Stra8 has not been identified in most teleost species except Southern catfish [ 18 ].…”