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Nucleic Acids Res
2000 Apr 15;288:1692-9. doi: 10.1093/nar/28.8.1692.
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An ATM homologue from Arabidopsis thaliana: complete genomic organisation and expression analysis.
Garcia V
,
Salanoubat M
,
Choisne N
,
Tissier A
.
???displayArticle.abstract??? ATM is a gene mutated in the human disease ataxia telangiectasia with reported homologues in yeast, Drosophila, Xenopus and mouse. Whenever mutants are available they all indicate a role of this gene family in the cellular response to DNA damage. Here, we present the identification and molecular characterisation of the first plant homologue of ATM. The genomic locus of AtATM ( Arabidopsis thaliana homologue of ATM ) spans over 30 kb and is transcribed into a 12 kb mRNA resulting from the splicing of 79 exons. It is a single copy gene and maps to the long arm of chromosome 3. Transcription of AtATM is ubiquitous and not induced by ionising radiation. The putative protein encoded by AtATM is 3856 amino acids long and contains a phosphatidyl inositol-3 kinase-like (Pi3k-l) domain and a rad3 domain, features shared by other members of the ATM family. The AtAtm protein is highly similar to Atm, with 67 and 45% similarity in the Pi3k-l and rad3 domains respectively. Interestingly, the N-terminal portion of the protein harbours a PWWP domain, which is also present in other proteins involved in DNA metabolism such as human mismatch repair enzyme Msh6 and the mammalian de novo methyl transferases, Dnmt3a/b.
Figure 2. (a) Alignment of the C-terminal region spanning the Pi3 kinase-like domain of AtAtm with six closely related members of the Atm family. The numbers on the right indicate the position of the residues for each protein. Amino acids identical to AtAtm are boxed in black. Pale and dark grey boxes highlight amino acid identities between two and three or more proteins respectively, AtAtm excluded. The alignment was performed with the PILEUP program (Genetics Computer Group, v.9.1). Vertical arrows indicate the three conserved residues of the kinase catalytic site, namely Asp 3681, Asn3686 and Asp3700 for AtAtm. (b) Schematic drawing for the alignment of the AtATM translation product to related protein in mammals (Atm, Atr), Drosophila melanogaster (Mei41) and yeast (Rad3, Tel1 and Mec1). Sequences were drawn to scale. Black boxes cover the Pi3-kinase-like region of strong homology, which is shared by all family members; boxes 1–5, the different homology domains between each protein and AtAtm; box 6, the region of similarity shared by AtAtm and Atm only. Thin lines for each sequence indicate region with no similarity (<20% identity). Alignments were performed agains thet AtAtm sequence with each of the family members using the GAP program (Genetics Computer Group, v.9.1). (c) Percentages of amino acid similarity and identity for the domains defined in (b) between the different Atm-related proteins. In each box, the first number represents the similarity and the second number the identity. (d) Alignment of the PWWP domain of the following proteins: AtAtm, Dnmt3b (accession number AAF04015), hMsh6 (accession number AAB39212), MMSET type I (accession number AAF23369), Caenorhabditis elegans similar to Sir2 ( accession number U97193) , and HDGF (accession number P51858) . The alignment was generated as in (a).
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