Genomes and Genes
Gene Symbol: mei-41
Description: meiotic 41
Alias: 4252, ATR, CG4252, DmATR, Dmel\CG4252, Dmmei41, MEI41, MEI41/FRP1, Mei-41, Mei-41/DATR, atr, fs(1)M37, mei-195, mei41, meiP41, mus(1)103, mus(1)104, mus-103, mus-104, mus103, mus104, meiotic 41, ATM-RAD3 related, CG4252-PA, drosophila ATR, mei-41-PA, meiotic-41
Species: fruit fly
- Chiolo I, Minoda A, Colmenares S, Polyzos A, Costes S, Karpen G. Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell. 2011;144:732-44 pubmed publisher..We propose that the spatial and temporal control of DSB repair in heterochromatin safeguards genome stability by preventing aberrant exchanges between repeats. ..
- Laurencon A, Purdy A, Sekelsky J, Hawley R, Su T. Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM/ATR. Genetics. 2003;164:589-601 pubmedATM/ATR kinases act as signal transducers in eukaryotic DNA damage and replication checkpoints...
- Sibon O, Kelkar A, Lemstra W, Theurkauf W. DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos. Nat Cell Biol. 2000;2:90-5 pubmed..We propose that centrosome inactivation is part of a damage-control system that blocks chromosome segregation when replication/damage checkpoint control fails. ..
- Ghabrial A, Schupbach T. Activation of a meiotic checkpoint regulates translation of Gurken during Drosophila oogenesis. Nat Cell Biol. 1999;1:354-7 pubmed..We also show that Vasa is a target of this meiotic checkpoint, and so may mediate the checkpoint-dependent translational regulation of Gurken. ..
- Sibon O, Laurencon A, Hawley R, Theurkauf W. The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. Curr Biol. 1999;9:302-12 pubmed..During early embryogenesis, however, this pathway is activated by developmental cues and is required for the transition from maternal to zygotic control of development at the MBT. ..
- Mason J, Champion L, Hook G. Germ-line effects of a mutator, mu2, in Drosophila melanogaster. Genetics. 1997;146:1381-97 pubmed..We propose that mu2 affects chromosomal structure during oogenesis, thereby modulating DNA repair. ..
- Chen Y, Pane A, Schupbach T. Cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila. Curr Biol. 2007;17:637-42 pubmed..In Drosophila, a meiotic checkpoint which monitors double-stranded DNA breaks and involves Drosophila ATR and Chk2 coordinates the meiotic cell cycle with signaling events that establish the axis of the egg and ..
- Sakaguchi A, Steward R. Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster. J Cell Biol. 2007;176:155-62 pubmed..Furthermore, in a double mutant of PR-Set7 and mei-41 (the fly ATR orthologue), the abnormalities of mitotic progression and the cyclin B protein level were rescued...
- McCaffrey R, St Johnston D, González Reyes A. Drosophila mus301/spindle-C encodes a helicase with an essential role in double-strand DNA break repair and meiotic progression. Genetics. 2006;174:1273-85 pubmed..Most of the oogenesis defects of mus301 mutants are suppressed by mutants in the checkpoint kinase Mei41 and in MeiW68, the Spo11 homolog that is thought to generate the dsDNA breaks that initiate recombination, ..
- Bi X, Gong M, Srikanta D, Rong Y. Drosophila ATM and Mre11 are essential for the G2/M checkpoint induced by low-dose irradiation. Genetics. 2005;171:845-7 pubmed..ATM and its regulator Mre11 are important for the checkpoint and that their roles become essential when animals are challenged with a low dose of X rays or when they have compromised checkpoint function of the ATM-related ATR kinase.
- Abdu U, Klovstad M, Butin Israeli V, Bakhrat A, Schupbach T. An essential role for Drosophila hus1 in somatic and meiotic DNA damage responses. J Cell Sci. 2007;120:1042-9 pubmed..These results demonstrate that hus1 is essential for the activation of the meiotic checkpoint and that hus1 is also required for the organization of the oocyte DNA, a function that might be independent of the meiotic checkpoint. ..
- Lee E, Trinh T, Shim H, Park S, Nguyen T, Kim M, et al. Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks. DNA Repair (Amst). 2012;11:741-52 pubmed publisherb>ATR and Chk1 are protein kinases that perform major roles in the DNA replication checkpoint that delays entry into mitosis in response to DNA replication stress by hydroxyurea (HU) treatment...
- Oikemus S, Queiroz Machado J, Lai K, McGinnis N, Sunkel C, Brodsky M. Epigenetic telomere protection by Drosophila DNA damage response pathways. PLoS Genet. 2006;2:e71 pubmed..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...
- Brodsky M, Sekelsky J, Tsang G, Hawley R, Rubin G. mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development. Genes Dev. 2000;14:666-78 pubmed..Similar mechanisms may account for the puzzling array of symptoms observed in humans with mutations in the ATM tumor suppressor gene. ..
- Iida T, Lilly M. missing oocyte encodes a highly conserved nuclear protein required for the maintenance of the meiotic cycle and oocyte identity in Drosophila. Development. 2004;131:1029-39 pubmed..Our data strongly suggest that the product of the missing oocyte gene acts in the oocyte nucleus to facilitate the execution of the unique cell cycle and developmental programs that produce the mature haploid gamete. ..
- Musarò M, Ciapponi L, Fasulo B, Gatti M, Cenci G. Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint. Nat Genet. 2008;40:362-6 pubmed publisher..The cell cycle arrest elicited by the DDR was alleviated by mutations in mei-41 (encoding ATR), mus304 (ATRIP), grp (Chk1) and rad50 but not by mutations in tefu (ATM)...
- Ciapponi L, Cenci G, Gatti M. The Drosophila Nbs protein functions in multiple pathways for the maintenance of genome stability. Genetics. 2006;173:1447-54 pubmedThe 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...
- Wichmann A, Jaklevic B, Su T. Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell death in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2006;103:9952-7 pubmed..This work establishes Drosophila as a model for p53-independent apoptosis, which is of potential therapeutic importance for inducing cell death in p53-deficient cancer cells. ..
- Masrouha N, Yang L, Hijal S, Larochelle S, Suter B. The Drosophila chk2 gene loki is essential for embryonic DNA double-strand-break checkpoints induced in S phase or G2. Genetics. 2003;163:973-82 pubmed..As mutations in human chk2 were linked to several cancers, these similarities point to the usefulness of the Drosophila model system. ..
- Xu J, Xin S, Du W. Drosophila Chk2 is required for DNA damage-mediated cell cycle arrest and apoptosis. FEBS Lett. 2001;508:394-8 pubmedChk2 is a major target of ataxia telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR)...
- Sekelsky J, Burtis K, Hawley R. Damage control: the pleiotropy of DNA repair genes in Drosophila melanogaster. Genetics. 1998;148:1587-98 pubmed
- Joyce E, McKim K. Drosophila PCH2 is required for a pachytene checkpoint that monitors double-strand-break-independent events leading to meiotic crossover formation. Genetics. 2009;181:39-51 pubmed publisher..intermediates: the delays in meiotic progression do not depend on DSB formation or on mei-41, the Drosophila ATR homolog, which is required for the checkpoint response to unrepaired DSBs...
- Mehrotra S, Maqbool S, Kolpakas A, Murnen K, Calvi B. Endocycling cells do not apoptose in response to DNA rereplication genotoxic stress. Genes Dev. 2008;22:3158-71 pubmed publisher..Similar mechanisms may operate during vertebrate development, with implications for cancer predisposition in certain tissues. ..
- Klattenhoff C, Bratu D, McGinnis Schultz N, Koppetsch B, Cook H, Theurkauf W. Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response. Dev Cell. 2007;12:45-55 pubmed..Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not ..
- Titen S, Golic K. Telomere loss provokes multiple pathways to apoptosis and produces genomic instability in Drosophila melanogaster. Genetics. 2008;180:1821-32 pubmed publisher..This aneuploidy may facilitate the continued escape of such cells from the normal checkpoint mechanisms. ..
- Hari K, Santerre A, Sekelsky J, McKim K, Boyd J, Hawley R. The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene. Cell. 1995;82:815-21 pubmed..Thus, the mei-41 gene of Drosophila may be considered to be a functional homolog of the human ATM gene. ..
- Abdu U, González Reyes A, Ghabrial A, Schupbach T. The Drosophila spn-D gene encodes a RAD51C-like protein that is required exclusively during meiosis. Genetics. 2003;165:197-204 pubmed..As there is no apparent ortholog of the meiosis-specific DMC1 gene in the Drosophila genome, and given their meiosis-specific requirement, we suggest that spn-B and spn-D may have a function comparable to DMC1. ..
- Sekelsky J, Brodsky M, Burtis K. DNA repair in Drosophila: insights from the Drosophila genome sequence. J Cell Biol. 2000;150:F31-6 pubmed
- Boyd J, Golino M, Nguyen T, Green M. Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens. Genetics. 1976;84:485-506 pubmed..The properties of the mutants generally conform to a pattern which has been established for related mutants in yeast. Additional properties of these mutants are summarized in Table 9. ..
- Klovstad M, Abdu U, Schupbach T. Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint. PLoS Genet. 2008;4:e31 pubmed publisher..In addition, Brca2 co-immunoprecipitates with the checkpoint protein Rad9, suggesting a direct role for Brca2 in the transduction of the meiotic recombination checkpoint signal. ..
- Sakaguchi A, Karachentsev D, Seth Pasricha M, Druzhinina M, Steward R. Functional characterization of the Drosophila Hmt4-20/Suv4-20 histone methyltransferase. Genetics. 2008;179:317-22 pubmed publisher..We find that even with this biochemical function, Suv4-20 is not required for survival and does not control position-effect variegation (PEV). ..
- Silva E, Lee B, Caceres L, Renouf D, Vilay B, Yu O, et al. A novel strategy for identifying mutations that sensitize Drosophila eye development to caffeine and hydroxyurea. Genome. 2006;49:1416-27 pubmed..We have mapped the cytological positions of huc(29D) and huc(95E) as a first step toward molecularly characterizing the relevant genes. ..
- Abdu U, Brodsky M, Schupbach T. Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk. Curr Biol. 2002;12:1645-51 pubmed..In addition, we found that p53 and mus304, the Drosophila ATR-IP homolog, are not required for the patterning defects caused by the meiotic DNA repair mutations...
- Rickmyre J, Dasgupta S, Ooi D, Keel J, Lee E, Kirschner M, et al. The Drosophila homolog of MCPH1, a human microcephaly gene, is required for genomic stability in the early embryo. J Cell Sci. 2007;120:3565-77 pubmed..In contrast to studies of human MCPH1, the ATR/Chk1-mediated DNA checkpoint is intact in Drosophila mcph1 mutants...
- Jaklevic B, Su T. Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae. Curr Biol. 2004;14:23-32 pubmed..okra (DmRAD54) mutants regulate the cell cycle but are deficient in repair of double strand breaks (DSB); mei-41 (DmATR) mutants cannot regulate the cell cycle and are deficient in DSB repair. All undergo radiation-induced apoptosis...
- Moskalev A, Plyusnina E, Shaposhnikov M. Radiation hormesis and radioadaptive response in Drosophila melanogaster flies with different genetic backgrounds: the role of cellular stress-resistance mechanisms. Biogerontology. 2011;12:253-63 pubmed publisher..observed in flies with mutations in autophagy genes (atg7, atg8a) but absent in flies with mutations in FOXO, ATM, ATR, and p53 homologues. The hormetic effect was revealed in Sirt2 mutant males but not in females...
- Ahmad K, Golic K. Telomere loss in somatic cells of Drosophila causes cell cycle arrest and apoptosis. Genetics. 1999;151:1041-51 pubmed..We conclude that Drosophila telomeres can be established and maintained by a mechanism that does not rely on the terminal DNA sequence. ..
- Flores C, Engels W. Microsatellite instability in Drosophila spellchecker1 (MutS homolog) mutants. Proc Natl Acad Sci U S A. 1999;96:2964-9 pubmed..Contrary to the case in mammalian cells, spel1 deficiency does not affect tolerance of flies to a methylating agent nor does it affect resistance to gamma-irradiation. ..
- Larocque J, Jaklevic B, Su T, Sekelsky J. Drosophila ATR in double-strand break repair. Genetics. 2007;175:1023-33 pubmed..Ataxia telangiectasia mutated (ATM) and ATR are essential for such cell-cycle control, but some observations suggest that they also play a direct role in DNA ..
- Lu W, Chapo J, Roig I, Abrams J. Meiotic recombination provokes functional activation of the p53 regulatory network. Science. 2010;328:1278-81 pubmed publisher..Our findings establish a physiological role for p53 in meiosis and suggest that tumor-suppressive functions may have been co-opted from primordial activities linked to recombination. ..
- Xu J, Du W. Drosophila chk2 plays an important role in a mitotic checkpoint in syncytial embryos. FEBS Lett. 2003;545:209-12 pubmed..J. Biol. Chem. 278 (2003) 8468-8475] in mammals, these observations suggest that polo might be a key target of Dmchk2 in regulating mitotic entry in response to DNA damage or replication block. ..
- Song Y, Mirey G, Betson M, Haber D, Settleman J. The Drosophila ATM ortholog, dATM, mediates the response to ionizing radiation and to spontaneous DNA damage during development. Curr Biol. 2004;14:1354-9 pubmed..Two protein kinases, ataxia-telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR), are sensors for DNA damage...
- Sakaguchi A, Joyce E, Aoki T, Schedl P, Steward R. The histone H4 lysine 20 monomethyl mark, set by PR-Set7 and stabilized by L(3)mbt, is necessary for proper interphase chromatin organization. PLoS ONE. 2012;7:e45321 pubmed
- Kurzhals R, Titen S, Xie H, Golic K. Chk2 and p53 are haploinsufficient with dependent and independent functions to eliminate cells after telomere loss. PLoS Genet. 2011;7:e1002103 pubmed publisher..In spite of these mechanisms to eliminate cells that have lost a telomere, we find that such cells can make a substantial contribution to differentiated adult tissues. ..
- Yamamoto A, Brodberg R, Banga S, Boyd J, Mason J. Recovery and characterization of hybrid dysgenesis-induced mei-9 and mei-41 alleles of Drosophila melanogaster. Mutat Res. 1990;229:17-28 pubmed..Hybrid dysgenesis-induced reversion of 2 mutants, mei-9RT1 and mei-41RT2, is associated with the loss of the P element from regions 4B and 14C respectively. ..
- Kasravi A, Walter M, Brand S, Mason J, Biessmann H. Molecular cloning and tissue-specific expression of the mutator2 gene (mu2) in Drosophila melanogaster. Genetics. 1999;152:1025-35 pubmed..The MU2 protein may be involved in controlling chromatin structure and thus may influence the processing of DNA DSBs. ..
- Ferreiro J, Sierra L, Comendador M. White-ivory assay of Drosophila melanogaster under deficient repair conditions. Environ Mol Mutagen. 1998;31:292-8 pubmed
- Zhou L, Steller H. Distinct pathways mediate UV-induced apoptosis in Drosophila embryos. Dev Cell. 2003;4:599-605 pubmed..This early UV response requires E2F but not mei-41 function and appears to be independent of DNA damage. ..
- Margulies L. A high level of hybrid dysgenesis in Drosophila: high thermosensitivity, dependence on DNA repair, and incomplete cytotype regulation. Mol Gen Genet. 1990;220:448-55 pubmed..The relatively high premature sterility of cross B DNA repair-deficient males, reared at 18 degrees C and aged at 21 degrees C, indicates that there is incomplete cytotype regulation in Hs subline hybrids. ..
- Morciano P, Zhang Y, Cenci G, Rong Y. A hypomorphic mutation reveals a stringent requirement for the ATM checkpoint protein in telomere protection during early cell division in Drosophila. G3 (Bethesda). 2013;3:1043-8 pubmed publisher..The amenability of Drosophila embryos to molecular and biochemical investigations ensures that this newly identified mutation will facilitate future studies of ATM in telomere maintenance. ..
- Carpenter A, Baker B. On the Control of the Distribution of Meiotic Exchange in DROSOPHILA MELANOGASTER. Genetics. 1982;101:81-9 pubmed
- Nakayama M, Maruyama S, Kanda H, Ohkita N, Nakano K, Ito F, et al. Relationships of Drosophila melanogaster RECQ5/QE to cell-cycle progression and DNA damage. FEBS Lett. 2006;580:6938-42 pubmed..These results suggest that RECQ5/QE interacts with components of the cell-cycle during its progression in response to DNA damage. ..
- Blower M, Daigle T, Kaufman T, Karpen G. Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components. PLoS Genet. 2006;2:e110 pubmed..We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization. ..
- Wei D, Rong Y. A genetic screen for DNA double-strand break repair mutations in Drosophila. Genetics. 2007;177:63-77 pubmed
- Vogel E. Tests for recombinagens in somatic cells of Drosophila. Mutat Res. 1992;284:159-75 pubmed
- Margulies L, Griffith C. The synergistic effect of X-rays and deficiencies in DNA repair in P-M hybrid dysgenesis in Drosophila melanogaster. Genet Res. 1991;58:15-26 pubmed..The exacerbation by X-rays of the effects of DNA repair deficiencies on genetic damage indicates that both repair mechanisms are required for processing DNA lesions induced by the combined effect of P activity and ionizing radiation. ..
- Fortini M, Skupski M, Boguski M, Hariharan I. A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol. 2000;150:F23-30 pubmed
- Meng Z, Capalbo L, Glover D, Dunphy W. Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1. Mol Biol Cell. 2011;22:2834-47 pubmed publisher..These phosphorylations promote binding of Chk1 to Claspin and ensuing activation of Chk1 by ATR. However, despite the importance of this regulatory process, the kinase responsible for these phosphorylations has ..
- Walworth N. Cell-cycle checkpoint kinases: checking in on the cell cycle. Curr Opin Cell Biol. 2000;12:697-704 pubmed..In addition, an appreciation that DNA damage arises as a natural consequence of cellular metabolism, including DNA replication itself, has influenced thinking regarding the nature of checkpoint pathways. ..
- Carpenter A, Sandler L. On recombination-defective meiotic mutants in Drosophila melanogaster. Genetics. 1974;76:453-75 pubmed
- Doronkin S, Djagaeva I, Beckendorf S. The COP9 signalosome promotes degradation of Cyclin E during early Drosophila oogenesis. Dev Cell. 2003;4:699-710 pubmed..Genetic interactions among CSN, SCF, and proteasome subunits further confirm CSN involvement in ubiquitin-mediated Cyclin E degradation. ..
- Inoue H, Baba H, Awano K, Yoshikawa K. Genotoxic effect of griseofulvin in somatic cells of Drosophila melanogaster. Mutat Res. 1995;343:229-34 pubmed..It is noted that (1) GF-fed larvae showed a developmental delay and (2) surviving adult flies had morphological abnormalities in their eyes and wings. ..
- Blythe S, Wieschaus E. Zygotic genome activation triggers the DNA replication checkpoint at the midblastula transition. Cell. 2015;160:1169-81 pubmed publisher..This suggests a model where the checkpoint functions as a feedback mechanism to remodel the cell cycle in response to nascent ZGA. ..
- Park J, Na H, Pyo J, Jeon H, Kim Y, Yoo M. Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila. Aging (Albany NY). 2015;7:307-18 pubmed..on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut...