UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior.

Cenci, Giovanni; Rawson, Robert B.; Belloni, Giorgio; Castrillón, Diego H.; Tudor, Mark; Petrucci, Rita; Goldberg, Michael L.; Wasserman, Steven A.; Gatti, Maurizio

doi:10.1101/gad.11.7.863

Cited by 121 publications

(95 citation statements)

References 55 publications

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“…Since DTAs and STAs are thought to be generated during G 1 and S-G 2 , respectively (de Lange 2002), each type of TA was considered as a single fusion event (Table 1). Telomeric associations observed in nbs 1 mutants involved all chromosome ends (data not shown), as observed in rad50, mre11, UbcD1, Su(var)205, cav, and woc mutants (Cenci et al 1997(Cenci et al , 2003Fanti et al 1998;Ciapponi et al 2004;Raffa et al 2005). Surprisingly, the frequency of TAs observed in nbs 1 mutant brains is approximately one-half of that found in either rad50 D5.1 or mre11 DC null mutants (Table 1; Ciapponi et al 2004).…”

Section: Resultsmentioning

confidence: 82%

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The Drosophila Nbs Protein Functions in Multiple Pathways for the Maintenance of Genome Stability

2006

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The 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. It has been previously shown that mutations in the Drosophila mre11 and rad50 genes cause both telomere fusion and chromosome breakage. Here, we have analyzed the role of the Drosophila nbs gene in telomere protection and the maintenance of chromosome integrity. Larval brain cells of nbs mutants display telomeric associations (TAs) but the frequency of these TAs is lower than in either mre11 or rad50 mutants. Consistently, Rad50 accumulates in the nuclei of wild-type cells but not in those of nbs cells, indicating that Nbs mediates transport of the Mre11/Rad50 complex in the nucleus. Moreover, epistasis analysis revealed that rad50 nbs, tefu (ATM) nbs, and mei-41 (ATR) nbs double mutants have significantly higher frequencies of TAs than either of the corresponding single mutants. This suggests that Nbs and the Mre11/Rad50 complex play partially independent roles in telomere protection and that Nbs functions in both ATR-and ATM-controlled telomere protection pathways. In contrast, analysis of chromosome breakage indicated that the three components of the MRN complex function in a single pathway for the repair of the DNA damage leading to chromosome aberrations.

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Section: Resultsmentioning

confidence: 82%

“…Chromosome cytology and analysis of telomeric fusions: DAPI-stained larval brain chromosome preparations were made as described previously (Cenci et al 1997). For each mutant or doubly mutant brain (Table 1), we examined between 40 and 60 metaphases for the presence of both TAs and chromosome breaks.…”

Section: Methodsmentioning

confidence: 99%

The Drosophila Nbs Protein Functions in Multiple Pathways for the Maintenance of Genome Stability

2006

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“…Recently, telomeric associations have been reported as a consequence of mutations in the UbcD1 gene in Drosophila melanogaster (Cenci et al, 1997), as well as mutations in a telomerase template in Tetrahymena thermophila (Kirk et al, 1997). To determine whether ATM function in¯uences TA, we examined metaphase spreads and found that RKO cells expressing dominant-negative fragments exhibited a 3 ± 6-fold higher frequency of cells with TA compared to parental and control RKO cells (Figure 1a).…”

Section: Resultsmentioning

confidence: 99%

Influence of ATM function on telomere metabolism

Smilenov

Morgan²,

Mellado

et al. 1997

Oncogene

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The ATM gene product, which is defective in the cancerprone disorder ataxia telangiectasia, has been implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination and cell cycle control. The ATM gene has homology with the TEL1 gene of yeast, mutations of which lead to shortened telomeres. To test the hypothesis that the ATM gene product is involved in telomere metabolism, we examined telomeric associations (TA), telomere length, and telomerase activity in human cells expressing either dominant-negative or complementing fragments of the ATM gene. The phenotype of RKO colorectal tumor cells expressing ATM fragments containing a leucine zipper (LZ) motif mimics that of ataxia telangiectasia (A-T) cells. These transfected RKO cells relative to transfected controls had a higher frequency of cells with TA and shortened telomeres, but no detectable change in telomerase activity. In addition, the percentage of cells with TA after gamma irradiation was higher in the transfected RKO cells with dominant negative activity of the ATM gene, compared to control cells. SV40 transformed ®broblasts derived from an A-T patient and transfected with a complementing carboxyl terminal kinase region of the ATM gene had a reduced frequency of cells with TA, with no eect on the telomere length or telomerase activity. The present studies using isogenic cells with manipulated ATM function demonstrate a role for the ATM gene product in telomere metabolism.

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“…Mutations in this gene cause high frequencies of telomeric fusions independent of the presence of HTT elements (46,47). It is not known whether the UbcD1 protein causes polyubiquitination and degradation of a telomere component or mono-ubiquitination resulting in modified allosteric conformation and activity of its substrate, nor is the substrate known.…”

Section: Proteins Associated With the Capmentioning

confidence: 99%

Drosophila telomeres: an exception providing new insights

2007

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SummaryDrosophila telomeres are comprised of DNA sequences that differ dramatically from those of other eukaryotes. Telomere functions, however, are similar to those found in telomerase-based telomeres, even though the underlying mechanisms may differ. Drosophila telomeres use arrays of retrotransposons to maintain chromosome length, while nearly all other eukaryotes rely on telomerase-generated short repeats. Regardless of the DNA sequence, several end-binding proteins are evolutionarily conserved. Away from the end, the Drosophila telomeric and subtelomeric DNA sequences are complexed with unique combinations of proteins that also modulate chromatin structure elsewhere in the genome. Maintaining and regulating the transcriptional activity of the telomeric retrotransposons in Drosophila requires specific chromatin structures, and while telomeric silencing spreads from the terminal repeats in yeast, the source of telomeric silencing in Drosophila is the subterminal arrays. However, the subterminal arrays in both species may be involved in telomere-telomere associations and/or communication.

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UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior.

Cited by 121 publications

References 55 publications

The Drosophila Nbs Protein Functions in Multiple Pathways for the Maintenance of Genome Stability

The Drosophila Nbs Protein Functions in Multiple Pathways for the Maintenance of Genome Stability

Influence of ATM function on telomere metabolism

Drosophila telomeres: an exception providing new insights

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