Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Cell Cycle
2011 Mar 15;106:989-98. doi: 10.4161/cc.10.6.15080.
Show Gene links
Show Anatomy links
Identification of dAven, a Drosophila melanogaster ortholog of the cell cycle regulator Aven.
Zou S, Chang J, LaFever L, Tang W, Johnson EL, Hu J, Wilk R, Krause HM, Drummond-Barbosa D, Irusta PM.
???displayArticle.abstract??? Aven is a regulator of the DNA-damage response and G2/M cell cycle progression. Overexpression of Aven is associated with poor prognosis in patients with childhood acute lymphoblastic leukemia and acute myeloid leukemia, and altered intracellular Aven distribution is associated with infiltrating ductal carcinoma and papillary carcinoma breast cancer subtypes. Although Aven orthologs have been identified in most vertebrate species, no Aven gene has been reported in invertebrates. Here, we describe a Drosophila melanogaster open reading frame (ORF) that shares sequence and functional similarities with vertebrate Aven genes. The protein encoded by this ORF, which we named dAven, contains several domains that are highly conserved among Aven proteins of fish, amphibian, bird and mammalian origins. In flies, knockdown of dAven by RNA interference (RNAi) resulted in lethality when its expression was reduced either ubiquitously or in fat cells using Gal4 drivers. Animals undergoing moderate dAven knockdown in the fat body had smaller fat cells displaying condensed chromosomes and increased levels of the mitotic marker phosphorylated histone H3 (PHH3), suggesting that dAven was required for normal cell cycle progression in this tissue. Remarkably, expression of dAven in Xenopus egg extracts resulted in G2/M arrest that was comparable to that caused by human Aven. Taken together, these results suggest that, like its vertebrate counterparts, dAven plays a role in cell cycle regulation. Drosophila could be an excellent model for studying the function of Aven and identifying cellular factors that influence its activity, revealing information that may be relevant to human disease.
Barlow,
Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I.
1998, Pubmed
Barlow,
Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I.
1998,
Pubmed Barlow,
Atm-deficient mice: a paradigm of ataxia telangiectasia.
1996,
Pubmed Bi,
Drosophila ATM and ATR checkpoint kinases control partially redundant pathways for telomere maintenance.
2005,
Pubmed Bi,
Telomere protection without a telomerase; the role of ATM and Mre11 in Drosophila telomere maintenance.
2004,
Pubmed Bi,
Drosophila ATM and Mre11 are essential for the G2/M checkpoint induced by low-dose irradiation.
2005,
Pubmed Brachmann,
The Drosophila bcl-2 family member dBorg-1 functions in the apoptotic response to UV-irradiation.
2000,
Pubmed Brodsky,
Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage.
2004,
Pubmed Brodsky,
mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development.
2000,
Pubmed Brown,
ATR disruption leads to chromosomal fragmentation and early embryonic lethality.
2000,
Pubmed Brown,
Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance.
2003,
Pubmed Canman,
The role of ATM in DNA damage responses and cancer.
1998,
Pubmed Chau,
Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1.
2000,
Pubmed Chehab,
Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53.
2000,
Pubmed Choi,
Aven overexpression: association with poor prognosis in childhood acute lymphoblastic leukemia.
2006,
Pubmed Clarke,
Cell-cycle control in the face of damage--a matter of life or death.
2009,
Pubmed Cliby,
Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints.
1998,
Pubmed Colussi,
Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery.
2000,
Pubmed Das,
Hyperoxia activates the ATR-Chk1 pathway and phosphorylates p53 at multiple sites.
2004,
Pubmed de Klein,
Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice.
2000,
Pubmed de Vries,
Grp/DChk1 is required for G2-M checkpoint activation in Drosophila S2 cells, whereas Dmnk/DChk2 is dispensable.
2005,
Pubmed
,
Xenbase Duffy,
GAL4 system in Drosophila: a fly geneticist's Swiss army knife.
2002,
Pubmed Elledge,
Cell cycle checkpoints: preventing an identity crisis.
1996,
Pubmed Esmaili,
Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export.
2010,
Pubmed
,
Xenbase Gatti,
The pathogenesis of ataxia-telangiectasia. Learning from a Rosetta Stone.
2001,
Pubmed Grönke,
Control of fat storage by a Drosophila PAT domain protein.
2003,
Pubmed Guo,
Aven-dependent activation of ATM following DNA damage.
2008,
Pubmed
,
Xenbase Guo,
Response of Xenopus Cds1 in cell-free extracts to DNA templates with double-stranded ends.
2000,
Pubmed
,
Xenbase Gutierrez,
Specialized hepatocyte-like cells regulate Drosophila lipid metabolism.
2007,
Pubmed Hari,
The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene.
1995,
Pubmed Herzog,
Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system.
1998,
Pubmed Hsu,
Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila.
2008,
Pubmed Hutchison,
Periodic DNA synthesis in cell-free extracts of Xenopus eggs.
1987,
Pubmed
,
Xenbase Hutchison,
The control of DNA replication in a cell-free extract that recapitulates a basic cell cycle in vitro.
1988,
Pubmed
,
Xenbase Igaki,
Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death.
2000,
Pubmed Jaklevic,
Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae.
2004,
Pubmed Kanuka,
Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator.
1999,
Pubmed Kashevsky,
The anaphase promoting complex/cyclosome is required during development for modified cell cycles.
2002,
Pubmed Kerzendorfer,
Human DNA damage response and repair deficiency syndromes: linking genomic instability and cell cycle checkpoint proficiency.
2009,
Pubmed Kumagai,
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase Kutuk,
Aven blocks DNA damage-induced apoptosis by stabilising Bcl-xL.
2010,
Pubmed Laurençon,
Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM/ATR.
2003,
Pubmed Lavin,
Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer.
2008,
Pubmed Lécuyer,
Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function.
2007,
Pubmed Lee,
In vivo p53 function is indispensable for DNA damage-induced apoptotic signaling in Drosophila.
2003,
Pubmed Liu,
Hormonal and nutritional regulation of insect fat body development and function.
2009,
Pubmed Margolis,
When the checkpoints have gone: insights into Cdc25 functional activation.
2004,
Pubmed
,
Xenbase Matsuoka,
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.
1998,
Pubmed Matsuoka,
Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro.
2000,
Pubmed Melchionna,
Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1.
2000,
Pubmed Meyn,
Ataxia-telangiectasia, cancer and the pathobiology of the ATM gene.
1999,
Pubmed Murray,
Cyclin synthesis drives the early embryonic cell cycle.
1989,
Pubmed
,
Xenbase Murray,
Cell cycle extracts.
1991,
Pubmed Oikemus,
Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect.
2004,
Pubmed Paydas,
Survivin and aven: two distinct antiapoptotic signals in acute leukemias.
2003,
Pubmed Perdiguero,
Regulation of Cdc25C activity during the meiotic G2/M transition.
2004,
Pubmed
,
Xenbase Peterson,
reaper is required for neuroblast apoptosis during Drosophila development.
2002,
Pubmed Quinn,
Buffy, a Drosophila Bcl-2 protein, has anti-apoptotic and cell cycle inhibitory functions.
2003,
Pubmed Reed,
The Drosophila gene morula inhibits mitotic functions in the endo cell cycle and the mitotic cell cycle.
1997,
Pubmed Rodriguez,
Dark is a Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily conserved death pathway.
1999,
Pubmed Roelofs,
Flying to a halt: Drosophila Aven arrests the cell cycle.
2011,
Pubmed Roos,
DNA damage-induced cell death by apoptosis.
2006,
Pubmed Rutkowski,
Phylogeny and function of the invertebrate p53 superfamily.
2010,
Pubmed Sancar,
Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints.
2004,
Pubmed Shiloh,
ATM and related protein kinases: safeguarding genome integrity.
2003,
Pubmed Sibon,
The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition.
1999,
Pubmed Silva,
ATM is required for telomere maintenance and chromosome stability during Drosophila development.
2004,
Pubmed Smith,
The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer.
2010,
Pubmed Smythe,
Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts.
1991,
Pubmed
,
Xenbase Sogame,
Drosophila p53 preserves genomic stability by regulating cell death.
2003,
Pubmed Song,
The Drosophila ATM ortholog, dATM, mediates the response to ionizing radiation and to spontaneous DNA damage during development.
2004,
Pubmed Takata,
Drosophila damaged DNA-binding protein 1 is an essential factor for development.
2004,
Pubmed Unsal-Kaçmaz,
Preferential binding of ATR protein to UV-damaged DNA.
2002,
Pubmed Wang,
An overactivated ATR/CHK1 pathway is responsible for the prolonged G2 accumulation in irradiated AT cells.
2003,
Pubmed Weinert,
DNA damage and checkpoint pathways: molecular anatomy and interactions with repair.
1998,
Pubmed Westphal,
atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in resistance to acute radiation toxicity.
1997,
Pubmed Wright,
Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control.
1998,
Pubmed Xu,
Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation.
2002,
Pubmed Xu,
Drosophila Chk2 is required for DNA damage-mediated cell cycle arrest and apoptosis.
2001,
Pubmed Xu,
Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma.
1996,
Pubmed Yoo,
Mcm2 is a direct substrate of ATM and ATR during DNA damage and DNA replication checkpoint responses.
2004,
Pubmed
,
Xenbase Zhou,
HAC-1, a Drosophila homolog of APAF-1 and CED-4 functions in developmental and radiation-induced apoptosis.
1999,
Pubmed
