Healing of Euchromatic Chromosome Breaks by Efficient <i>de novo</i> Telomere Addition in <i>Drosophila melanogaster</i>

Titen, Simon; Golic, Kent G.

doi:10.1534/genetics.109.109934

Cited by 20 publications

(29 citation statements)

References 15 publications

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“…For instance, if chromosome healing was very inefficient except at a few sites, it might account for these results. However, previous results show that healing can occur at many sites in heterochromatin and euchromatin (Mason et al 1984;Levis 1989;Biessmann et al 1990;Tower et al 1993;Ahmad and Golic 1998;Mikhailovsky et al 1999;Titen and Golic 2010;Beaucher et al 2012;Titen et al 2014).…”

Section: Discussionmentioning

confidence: 97%

Preferential Breakpoints in the Recovery of Broken Dicentric Chromosomes inDrosophila melanogaster

Hill¹,

Golic

2015

Genetics

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We designed a system to determine whether dicentric chromosomes in Drosophila melanogaster break at random or at preferred sites. Sister chromatid exchange in a Ring-X chromosome produced dicentric chromosomes with two bridging arms connecting segregating centromeres as cells divide. This double bridge can break in mitosis. A genetic screen recovered chromosomes that were linearized by breakage in the male germline. Because the screen required viability of males with this X chromosome, the breakpoints in each arm of the double bridge must be closely matched to produce a nearly euploid chromosome. We expected that most linear chromosomes would be broken in heterochromatin because there are no vital genes in heterochromatin, and breakpoint distribution would be relatively unconstrained. Surprisingly, approximately half the breakpoints are found in euchromatin, and the breakpoints are clustered in just a few regions of the chromosome that closely match regions identified as intercalary heterochromatin. The results support the Laird hypothesis that intercalary heterochromatin can explain fragile sites in mitotic chromosomes, including fragile X. Opened rings also were recovered after male larvae were exposed to X-rays. This method was much less efficient and produced chromosomes with a strikingly different array of breakpoints, with almost all located in heterochromatin. A series of circularly permuted linear X chromosomes was generated that may be useful for investigating aspects of chromosome behavior, such as crossover distribution and interference in meiosis, or questions of nuclear organization and function.KEYWORDS dicentric chromosome; intercalary heterochromatin; fragile X; FLP D ROSOPHILA is noted for a combination of facile genetics and high-resolution cytology that allows the recovery and characterization of a variety of chromosome rearrangements. Simple structural changes such as duplications, deficiencies, inversions, and translocations are readily produced through a variety of classical and modern techniques. More complex rearrangements such as balancers, compound chromosomes, and ring chromosomes also have been generated. Ring chromosomes historically have been of interest for a number of unique properties, such as a propensity for loss during early embryonic mitoses and dominant zygotic lethality (Leigh 1976;Ashburner et al. 2005). Despite their "instability," ring chromosome stocks can be remarkably stable, with very few reported instances of spontaneous opening into linear chromosomes.In this work, we produced a number of linearized ring chromosomes. One goal was to determine whether there are preferred sites of breakage for dicentric chromosomes. Although we have previously shown that dicentric Y, 3, and 4 chromosomes can break and heal in the male germline and be recovered in offspring, these chromosomes allowed little opportunity to determine whether there were preferred sites of breakage (Ahmad and Golic 1998; Golic 2008, 2010;Titen et al. 2014). In the case of the Y chromosome, low r...

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Section: Discussionmentioning

confidence: 97%

Preferential Breakpoints in the Recovery of Broken Dicentric Chromosomes inDrosophila melanogaster

Hill¹,

Golic

2015

Genetics

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“…These events include mobilization of P elements inserted near the telomere (Tower et al, 1993), breakage of dicentric chromosomes during anaphase (Ahmad and Golic, 1998; Titen and Golic, 2010), and induction of an enzymatic cut in a P element construct inserted in the telomere region (Gao et al, 2010; Beaucher et al, 2012). A recent analysis of de novo telomere formation at double strand breaks (DSBs) generated by the enzymatic cut method showed that neotelomere formation occurs rather frequently in wild type males and is facilitated by partial disruption of DNA repair functions such as those of Mu2/MDC1, Rad51, ATRIP, Nbs, or ATM (Beaucher et al, 2012).…”

Section: Drosophila Telomeres Are Epigenetically Determined Structuresmentioning

confidence: 99%

Organization and Evolution of Drosophila Terminin: Similarities and Differences between Drosophila and Human Telomeres

Raffa¹,

Cenci²,

Ciapponi³

et al. 2013

Front. Oncol.

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Drosophila lacks telomerase and fly telomeres are elongated by occasional transposition of three specialized retroelements. Drosophila telomeres do not terminate with GC-rich repeats and are assembled independently of the sequence of chromosome ends. Recent work has shown that Drosophila telomeres are capped by the terminin complex, which includes the fast-evolving proteins HOAP, HipHop, Moi, and Ver. These proteins, which are not conserved outside Drosophilidae and closely related Diptera, localize and function exclusively at telomeres, protecting them from fusion events. Other proteins required to prevent end-to-end fusion in flies include HP1, Eff/UbcD1, ATM, the components of the Mre11-Rad50-Nbs (MRN) complex, and the Woc transcription factor. These proteins do not share the terminin properties; they are evolutionarily conserved non-fast-evolving proteins that do not accumulate only at telomeres and do not serve telomere-specific functions. We propose that following telomerase loss, Drosophila rapidly evolved terminin to bind chromosome ends in a sequence-independent manner. This hypothesis suggests that terminin is the functional analog of the shelterin complex that protects human telomeres. The non-terminin proteins are instead likely to correspond to ancestral telomere-associated proteins that did not evolve as rapidly as terminin because of the functional constraints imposed by their involvement in diverse cellular processes. Thus, it appears that the main difference between Drosophila and human telomeres is in the protective complexes that specifically associate with the DNA termini. We believe that Drosophila telomeres offer excellent opportunities for investigations on human telomere biology. The identification of additional Drosophila genes encoding non-terminin proteins involved in telomere protection might lead to the discovery of novel components of human telomeres.

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“…TDs with neotelomeres have also been recovered from mutational events occurred in the male germline. These events include X-ray induced breaks in the Dp(1;f)1187 mini-chromosome, 16 the mobilization of a P element located near the telomere, 17 breakage of dicentric chromosomes generated by site specific recombination, 18,19 and induction of an enzymatic cut in an I-Sce1 site placed within a P element construct inserted near the telomere. 20 Collectively, these results demonstrate that the HTT elements are not required for fly telomere assembly and that virtually any DNA sequence has the ability to form the nucleoprotein complex that protects the ends of Drosophila chromosomes.…”

Section: Termininmentioning

confidence: 99%

“…[22][23][24][25] Human telomeres terminate with a single stranded overhang of tandem TTAGGG repeats, which loops back invading the to the extremities of various types of terminally deleted chromosomes demonstrating that these proteins bind chromosome ends independently of the sequence of terminal DNA. 19,20,33,34 It should be noted that despite its direct interaction with HOAP, HipHop and Moi, HP1 should not be considered as a terminin component, because it does not localize exclusively at telomeres and has multiple telomere-unrelated functions (reviewed in refs. 46 and 47).…”

Section: Telomere Capping Complexes In Organisms With Telomerasementioning

confidence: 99%

Terminin: A protein complex that mediates epigenetic maintenance ofDrosophilatelomeres

Raffa¹,

Ciapponi²,

Cenci³

et al. 2011

Nucleus

124

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Healing of Euchromatic Chromosome Breaks by Efficient de novo Telomere Addition in Drosophila melanogaster

Cited by 20 publications

References 15 publications

Preferential Breakpoints in the Recovery of Broken Dicentric Chromosomes inDrosophila melanogaster

Preferential Breakpoints in the Recovery of Broken Dicentric Chromosomes inDrosophila melanogaster

Organization and Evolution of Drosophila Terminin: Similarities and Differences between Drosophila and Human Telomeres

Terminin: A protein complex that mediates epigenetic maintenance ofDrosophilatelomeres

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