Disease relevance of tefu

• Pharmacological inhibitors and RNA interference were used to demonstrate that ionizing-radiation-induced upregulation of TAF1-3 and TAF1-4 splicing in S2 cells was mediated by the ATM (ataxia-telangiectasia mutated) DNA damage response kinase and checkpoint kinase 2 (CHK2), a known ATM substrate [1].
• At a cellular level, spontaneous telomere fusions and other chromosomal abnormalities are common in atm larval neuroblasts, suggesting a conserved and essential role for dATM in the maintenance of normal telomeres and chromosome stability [2].

High impact information on tefu

• In the absence of hydroxyurea, a G2 checkpoint delay occurred in cnd2-1 mutants in a manner dependent on Cds1 and ATM-like Rad3, but not Chk1 (refs 10-13), before the mitotic condensation defect [3].
• Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect [4].
• We propose that recognition of chromosome ends by ATM prevents telomere fusion and apoptosis by recruiting chromatin-modifying complexes to telomeres [4].
• ATM and ATR Pathways Signal Alternative Splicing of Drosophila TAF1 Pre-mRNA in Response to DNA Damage [1].
• We conducted genetic and cytological studies on Drosophila atm and mre11 knockout mutants and discovered a telomere defect that was more severe than in any of the non-Drosophila systems studied [5].

Biological context of tefu

• The Mre11/Rad50/Nbs (MRN) complex and the two protein kinases ATM and ATR play critical roles in the response to DNA damage and telomere maintenance in mammalian systems [6].
• It has been previously shown that mutations in the Drosophila mre11 and rad50 genes cause both telomere fusion and chromosome breakage [6].
• We examined the roles of the Drosophila atm and atr-atrip DNA damage response pathways and the nbs homolog in DNA damage responses and telomere protection [7].
• Drosophila nbs is required for both atm- and atr-dependent DNA damage responses and acts in these pathways during DNA repair [7].
• The telomere fusion phenotype of nbs is consistent with defects in each of these activities [7].

Anatomical context of tefu

• Rescue experiments using a GAL4-driven pUAS transgene demonstrate that tef corresponds to predicted Berkeley Drosophila Genome Project (BDGP) gene CG8961 and that tef expression is required in the male germ line prior to spermatocyte stage S4 [8].

Associations of tefu with chemical compounds

• Here we report the generation of a null allele of mei-41, Drosophila ATM/ATR homolog, and the use of it to document a semidominant effect on a larval mitotic checkpoint and methyl methanesulfonate (MMS) sensitivity [9].
• The median effective dose (ED50) for halothane was 0.0096 atm in females and 0.0091 atm in males of the bw;st;svn strain, while in the Eth-29 strain the ED50 was 0.0148 atm in both sexes [10].

Other interactions of tefu

• Su(var)2-HP2 mutant larvae show a wide variety of mitotic abnormalities, but not the telomere fusion seen in larvae deficient for HP1 [11].

References