Disease relevance of TEL1

• It has been shown that phosphorylation of Rad53 is controlled by Mec1 and Tel1, members of the subfamily of ataxia-telangiectasia mutated (ATM) kinases [1].
• TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1 [2].
• TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene [3].

High impact information on TEL1

• The Mre11 nuclease and the ATM-related Tel1 kinase are the first proteins detected at DSBs [4].
• The rearrangements were primarily deletion of a portion of a chromosome arm along with TEL1-dependent addition of a new telomere. tel1 mutations increased the proportion of translocations observed, and in some cases showed synergistic interactions when combined with mutations that increased the genome rearrangement rate [5].
• We have cloned tel1+, another fission yeast ATM homologue, and found that a tel1rad3 double mutant lost all telomeric DNA sequences [6].
• Mutations in the gene TEL1 result in shortened telomeres [3].
• The closest homolog to TEL1 is the human ataxia telangiectasia gene [3].

Biological context of TEL1

• These data argue that Mre11p and Tel1p affect telomere length by promoting telomerase recruitment to telomeres, whereas Mec1p has only a minor role in telomerase recruitment in a TEL1 cell [7].
• Hyperactivation of the yeast DNA damage checkpoint by TEL1 and DDC2 overexpression [8].
• Similar chromosome rearrangements have been detected in mammalian cells with mutations in ATM (related to TEL1) and ATR (related to MEC1) and in mammalian cells that approach cell crisis [9].
• Finally, Xrs2 is phosphorylated after phleomycin treatment in a TEL1-dependent manner during S phase, whereas no significant Xrs2 phosphorylation is detected after MMS treatment [10].
• Tel1 and the C terminus of Xrs2 are similarly involved in cell survival and Rad53 phosphorylation after DNA damage [11].

Anatomical context of TEL1

• It affects growth, transcriptional activation, repression and elongation, telomere length regulation, telomeric position effect, rDNA silencing, meiotic differentiation, DNA repair, chromosome segregation, and cell wall organization [12].
• Both proteins have been implicated in telomere length regulation, insulin signalling and centrosome function [13].

Associations of TEL1 with chemical compounds

• Budding Yeast Sae2 is an In Vivo Target of the Mec1 and Tel1 Checkpoint Kinases During Meiosis [14].

Physical interactions of TEL1

• A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation [15].

Regulatory relationships of TEL1

• We also demonstrate that overexpression of TEL1 suppresses the ts growth defect and DNA damage sensitivity of rfc5-1 mutants and restores phosphorylation of Rad53 and RNR3 induction in response to DNA damage in rfc5-1 [1].
• The Mre11 complex controls the ATM/Tel1 signaling pathway in response to double-strand break (DSB) induction [16].
• We found that UV irradiation in G(1) in the absence of Mec1 activates a Tel1/MRX-dependent checkpoint, which specifically inhibits the metaphase-to-anaphase transition [17].
• This may be due to other factors than Rap1p having influence on the telomere length regulation [18].
• Second, Tel1 can activate the checkpoint response to DSBs independently of Mec1, although its signalling activity only becomes apparent when several DSBs are generated [19].

Other interactions of TEL1

• We report here that multiple Mec1/Tel1 consensus [S/T]Q sites within Rad9 are phosphorylated in response to DNA damage [20].
• In asynchronous cultures, Rad9 hyperphosphorylation was dependent on MEC1 and TEL1, homologues of the ATR and ATM genes [21].
• New function of CDC13 in positive telomere length regulation [22].
• Budding yeast Tel1 is required both for telomere metabolism and for a Rad53-dependent checkpoint responding to unprocessed double-strand breaks [23].
• The functions of budding yeast Sae2 in the DNA damage response require Mec1- and Tel1-dependent phosphorylation [24].

Analytical, diagnostic and therapeutic context of TEL1

• Sequence analysis of TEL1 indicates that it encodes a very large (322 kDa) protein with amino acid motifs found in phosphatidylinositol/protein kinases [3].

References