Retrotransposons Provide an Evolutionarily Robust Non-Telomerase Mechanism to Maintain Telomeres

Pardue, Mary Lou; DeBaryshe, P. G.

doi:10.1146/annurev.genet.38.072902.093115

Cited by 205 publications

(198 citation statements)

References 108 publications

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“…Presumably the overgrowing tissue of the fly tumors actively induces tracheal recruitment, but how this happens in the deeply embedded cells of a compact nTSG tumor has not yet been analyzed. Telomere renewal and end protection are telomerase-independent in the fly (Pardue and DeBaryshe 2003) and are unlikely to impose a senescent limit on fly cell proliferation, although control of telomere length in nTSG mutants has not been explored.…”

Section: How Closely Do the Fly Tumors Resemble Human Tumors?mentioning

confidence: 99%

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Bilder¹

2004

Genes Dev.

517

510

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Mammalian epithelial tumors lose polarity as they progress toward malignancy, but whether polarity loss might causally contribute to cancer has remained unclear. In Drosophila, mutations in the "neoplastic tumor suppressor genes" (nTSGs) scribble, discs-large, and lethal giant larvae disrupt polarity of epithelia and neuroblasts, and simultaneously induce extensive overproliferation of these cells, which exhibit malignant-like characteristics. Herein I review what is known about the role of the fly nTSGs in controlling cell polarity and cell proliferation. Incorporating data from mammalian studies, I consider how polarity and proliferation can be coupled, and how disruption of polarity could promote cancer.

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Section: How Closely Do the Fly Tumors Resemble Human Tumors?mentioning

confidence: 99%

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Bilder¹

2004

Genes Dev.

517

510

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“…They have been involved in chromosome rearrangements during the evolution of a wide variety of organisms, and retrotransposition has generated at least half of the human and mouse genomes. Particularly, retrotransposition has generated intronless copies of cellular genes (retrogenes), some of them, for example, forming a family of Y-chromosomal genes expressed exclusively in the testis and implicated in male fertility in human (Lahn et al, 2002 (Pardue and DeBaryshe, 2003;Brandt et al, in press).…”

Section: Diversity Of Transposable Elements (Tes) In Fishmentioning

confidence: 99%

Genome evolution and biodiversity in teleost fish

2004

Heredity

602

430

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Teleost fish, which roughly make up half of the extant vertebrate species, exhibit an amazing level of biodiversity affecting their morphology, ecology and behaviour as well as many other aspects of their biology. This huge variability makes fish extremely attractive for the study of many biological questions, particularly of those related to evolution. New insights gained from different teleost species and sequencing projects have recently revealed several peculiar features of fish genomes that might have played a role in fish evolution and speciation. There is now substantial evidence that a round of tetraploidization/rediploidization has taken place during the early evolution of the ray-finned fish lineage, and that hundreds of duplicate pairs generated by this event have been maintained over hundreds of millions of years of evolution. Differential loss or subfunction partitioning of such gene duplicates might have been involved in the generation of fish variability. In contrast to mammalian genomes, teleost genomes also contain multiple families of active transposable elements, which might have played a role in speciation by affecting hybrid sterility and viability. Finally, the amazing diversity of sex determination systems and the plasticity of sex chromosomes observed in teleost might have been involved in both pre-and postmating reproductive isolation. Comparison of data generated by current and future genome projects as well as complementary studies in other species will allow one to approach the molecular and evolutionary mechanisms underlying genome diversity in fish, and will certainly significantly contribute to our understanding of gene evolution and function in humans and other vertebrates. Heredity (2005) 94, 280-294.

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“…LINE1 elements have a less stringent preference for the sequence TTTTA, which results in integrations into gene-poor regions (6). Other retroelements target genomic loci through protein-protein interactions, to insert at pol III promoters (7), into telomeric elements (8), or into heterochromatin regions (9).…”

mentioning

confidence: 99%

Insertion of group II intron retroelements after intrinsic transcriptional terminators

Robart

Seo²,

Zimmerly³

2007

Proc. Natl. Acad. Sci. U.S.A.

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Mobile DNAs use many mechanisms to minimize damage to their hosts. Here we show that a subclass of group II introns avoids host damage by inserting directly after transcriptional terminator motifs in bacterial genomes (stem-loops followed by Ts). This property contrasts with the site-specific behavior of most group II introns, which insert into homing site sequences. Reconstituted ribonucleoprotein particles of the Bacillus halodurans intron B.h.I1 are shown to reverse-splice into DNA targets in vitro but require the DNA to be single-stranded and fold into a stem-loop analogous to the RNA structure that forms during transcription termination. Recognition of this DNA stem-loop motif accounts for in vivo target specificity. Insertion after terminators is a previously unrecognized strategy for a selfish DNA because it prevents interruption of coding sequences and restricts expression of the mobile DNA after integration.reverse transcriptase ͉ ribozyme ͉ mobile DNA ͉ bacteria R eduction of host damage is a basic principle of survival for selfish DNAs. The most common mechanisms involve suppression of transcription and translation, and integration into comparatively innocuous sites (1-4). Among retroelements, for example, R2 elements insert site-specifically into defined sequences within rDNA arrays while leaving most rDNAs intact (5). LINE1 elements have a less stringent preference for the sequence TTTTA, which results in integrations into gene-poor regions (6). Other retroelements target genomic loci through protein-protein interactions, to insert at pol III promoters (7), into telomeric elements (8), or into heterochromatin regions (9).Group II intron retroelements avoid host damage in two ways. First, the introns splice out of interrupted sequence at the RNA level to reconstitute functional coding sequence. Second, the introns insert site-specifically into compatible targets through retrohoming, thereby limiting potential targets. The mechanism of retrohoming is well characterized and is carried out by a ribonucleoprotein (RNP) complex composed of excised intron lariat and intron-encoded protein (IEP). The process is initiated by reverse splicing of lariat RNA into the top strand of a DNA target. The bottom strand is cleaved by the endonuclease domain of the IEP, and the integrated intron is reverse transcribed by the IEP, using the cleaved DNA as a primer. Repair processes complete the insertion steps (10-12).Normally, retrohoming of group II introns is highly sitespecific because of an Ϸ20-to 35-bp target sequence. Thirteen positions of the DNA target are recognized by base pairings between the intron RNA and the DNA exons via the interactions IBS1-EBS1, IBS2-EBS2 (intron and exon binding sites 1 and 2; 6 bp each), and either ␦-␦Ј (IIA introns; 1 bp) or IBS3-EBS3 (IIB, IIC introns; 1 bp). Additional target-specificity comes from IEP recognition of upstream exon DNA sequences Ϫ23 to Ϫ1 and downstream exon sequences ϩ4 to ϩ9 (11,13,14).In contrast to such site-specificity, introns of the phylogenetic subclass ''b...

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Retrotransposons Provide an Evolutionarily Robust Non-Telomerase Mechanism to Maintain Telomeres

Cited by 205 publications

References 108 publications

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Genome evolution and biodiversity in teleost fish

Insertion of group II intron retroelements after intrinsic transcriptional terminators

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