The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene

Hari, Kumar; Santerre, Anne; Sekelsky, Jeff; McKim, Kim S.; Boyd, James B.; Hawley, R. Scott

doi:10.1016/0092-8674(95)90478-6

Cited by 266 publications

(179 citation statements)

References 39 publications

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“…The essential MEC1/ ERS1 protein is required for the majority of responses observed in S. cerevisiae including the DNA replication and damage checkpoint pathways, transcriptional activation of DNA damage-responsive genes, meiotic recombination and DNA repair (Weinert et al, 1994;Kato and Ogawa, 1994). Structural and functional homologs of MEC1 include the Drosophila melanogaster Mei-41 protein, the S. Pombe Rad3 protein, and the mammalian AT-and Rad3-related ATR/FRP1 protein (Hari et al, 1995;Bentley et al, 1996;Cimprich et al, 1996). The closest homolog to ATM in sequence similarity is the S. cerevisiae TEL1 gene product, deletions of which results in the shortening of telomeres (Morrow et al, 1995;Greenwell et al, 1995).…”

Section: Atm Proteinmentioning

confidence: 99%

The role of ATM in DNA damage responses and cancer

1998

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Section: Atm Proteinmentioning

confidence: 99%

The role of ATM in DNA damage responses and cancer

1998

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“…It has been suggested that an ATM-like protein has a critical role in maintaining chromosome condensation in the vicinity of recombination intermediates (Hawley and Friend, 1996). In support of the role of ATM gene in chromosome condensation, it has been reported that mei-41 mutants of Drosophila melanogaster (homologue of ATM gene) exhibit di used chromatin (Hari et al, 1995). The ATM gene encodes a protein kinase that is distantly related to the yeast MEC1 and TEL1 proteins that function in maintaining the integrity of telomeres (Greenwell et al, 1995;Morrow et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

ATM function and telomere stability

2002

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Accumulation of DNA damage has been associated with the onset of senescence and predisposition to cancer. The gene responsible for ataxia telangiectasia (A-T) is ATM (ataxia-telangiectasia mutant), a master controller of cellular pathways and networks, orchestrating the responses to a speci®c type of DNA damage: the double strand break. Based on the homology of the human ATM gene to the TEL1, MEC1 and rad3 genes of yeast, it has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells. While ATM has both nuclear and cytoplasmic functions, this review will focus on its roles in telomere metabolism and how ATM and telomeres serve as controllers of cellular responses to DNA damage.

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“…In addition, the PIK family includes the TOR proteins, which are targets of the FKBP-rapamycin complex (Brown and Schreiber, 1996;Hall, 1996), and the ataxia telangiectasia gene product, ATM (Savitsky et al, 1995). A subset of the PIK family contains an additional region of homology termed the rad3 homologous region, and this subfamily includes the S. cerevisiae MEC1 and TEL1 (Greenwell et al, 1995;Morrow et al, 1995) and the Drosophila mei-41 gene product (Hari et al, 1995). Mutants in mec1, mei-41 and rad3 all display increased radiation sensitivity and are de®cient in cell cycle checkpoints which prevent mitosis in the presence of unreplicated or damaged DNA.…”

Section: Introductionmentioning

confidence: 99%

ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK

et al. 1999

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ATR is a large, 4300 kDa protein containing a carboxy-terminus kinase domain related to PI-3 kinase, and is homologous to the ATM gene product in human cells and the rad3/MEC1 proteins in yeast. These proteins, together with the DNA-PK, are part of a new family of PI-3 kinase related proteins. All members of this family play important roles in checkpoints which operate to permit cell survival following many forms of DNA damage. We have expressed ATR protein in HEK293 cells and puri®ed the protein to near-homogeneity. We show that pure ATR is a protein kinase which is activated by circular single-stranded, doublestranded or linear DNA. Thus ATR is a new member of a sub-family of PIK related kinases, founded by the DNA-PK, which are activated in the presence of DNA. Unlike DNA-PK, ATR does not appear to require Ku proteins for its activation by DNA. We show directly that, like ATM and DNA-PK, ATR phosphorylates the genome surveillance protein p53 on serine 15, a site which is up-regulated in response to DNA damage. In addition, we ®nd that ATR has a substrate speci®city similar to, but unique from, the DNA-PK in vitro, suggesting that these proteins have overlapping but distinct functions in vivo. Finally, we ®nd that the kinase activity of ATR in the presence and absence of DNA is suppressed by ca eine, a compound which is known to induce loss of checkpoint control. Our results are consistent with the notion that ATR plays a role in monitoring DNA structure and phosphorylation of proteins involved in the DNA damage response pathways.

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The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene

Cited by 266 publications

References 39 publications

The role of ATM in DNA damage responses and cancer

The role of ATM in DNA damage responses and cancer

ATM function and telomere stability

ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK

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