Involvement of cDNA in homologous recombination between Ty elements in Saccharomyces cerevisiae.

Melamed, C; Nevo, Yoram; Kupiec, Martin

doi:10.1128/mcb.12.4.1613

Cited by 58 publications

(52 citation statements)

References 38 publications

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“…Tf2-neo not only has a decreased mobilization frequency but also moves mostly by re- combination of Tf2-neo cDNA with endogenous Tf2 elements. This recombination of cDNA with endogenous elements has been observed for other yeast retrotransposons (2,24,31,39,52), but never as the major mobilization pathway for the wt element in question. It is formally possible that the high proportion of cDNA recombination events occurs as a result of overexpression of the Tf2-neo element; however, yeast retrotransposon studies using overexpression systems have generally reflected the biology of the endogenous elements (15,26).…”

Section: Discussionmentioning

confidence: 93%

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Schizosaccharomyces pombe Retrotransposon Tf2 Mobilizes Primarily through Homologous cDNA Recombination

Hoff

Levin

Boeke

1998

Molecular and Cellular Biology

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The Tf2 retrotransposon, found in the fission yeast Schizosaccharomyces pombe, is nearly identical to its sister element, Tf1, in its reverse transcriptase-RNase H and integrase domains but is very divergent in the gag domain, the protease, the 5 untranslated region, and the U3 domain of the long terminal repeats. It has now been demonstrated that a neo-marked copy of Tf2 overexpressed from a heterologous promoter can mobilize into the S. pombe genome and produce true transposition events. However, the Tf2-neo mobilization frequency is 10-to 20-fold lower than that of Tf1-neo, and 70% of the Tf2-neo events are homologous recombination events generated independently of a functional Tf2 integrase. Thus, the Tf2 element is primarily dependent on homologous recombination with preexisting copies of Tf2 for its propagation. Finally, production of Tf2-neo proteins and cDNA was also analyzed; surprisingly, Tf2 was found to produce its reverse transcriptase as a single species in which it is fused to protease, unlike all other retroviruses and retrotransposons.Transposable elements constitute up to 50% of the eukaryotic genome (51, 53). Though they can act as positive forces in the evolution of an organism, both by providing part of the chromosomal architecture (30) and by providing a source of mutagens (1), they also represent a burden on the host cell genome and a potential threat to host cell viability, should they "jump" into an essential region of the genome or mediate a rearrangement thereof. Different transposable elements have developed different means to balance their survival with that of the host cell by controlling their spread within the genome. Most balancing mechanisms described thus far appear to involve control of either transposon expression or target site selection (9). These mechanisms often rely on host-specific factors, such as transcription factors (10, 27), splicing factors (47), and chromatin organization (58). Characterization of different transposable elements can therefore reveal both new mechanisms for control of element mobility and new hostelement interactions.Long terminal repeat (LTR)-type retrotransposons (hereafter referred to simply as retrotransposons) have been isolated from many different eukaryotic organisms, including fruit flies, maize, and the yeast Saccharomyces cerevisiae (6,23,(48)(49)(50). Retrotransposons resemble retroviruses in both genome structure and replication mechanism (9). Like retroviruses, they possess terminally redundant ends (LTRs), a primer binding site for the initiation of reverse transcription, and a polypurine tract that serves as the primer in second-strand synthesis of the cDNA copy of the element. A single mRNA encodes proteins homologous to the retroviral structural proteins capsid (CA) and, sometimes, nucleocapsid (NC) and to the retroviral enzymes protease (PR), reverse transcriptase-RNase H (RT), and integrase (IN). These proteins coassemble to form retrovirus-like particles in which reverse transcription of an RNA intermediate takes place. The res...

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Section: Discussionmentioning

confidence: 93%

“…In yeast, this has resulted in very-low-frequency homologous recombination of retrotransposon cDNA with preexisting genomic copies of its parent element, in addition to normal transposition (39). This integrase-independent pathway relies on host cell recombination machinery (43,52).…”

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confidence: 99%

Schizosaccharomyces pombe Retrotransposon Tf2 Mobilizes Primarily through Homologous cDNA Recombination

Hoff

Levin

Boeke

1998

Molecular and Cellular Biology

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“…Based on the high amino acid sequence identity among the 12 copies of Tf2 (99%), we infer that other Tf2 elements mobilize by recombination. A similar mechanism of cDNA mobilization has been observed for Ty elements in S. cerevisiae [36,37]. Mobilization of Tf2 by cDNA recombination to existing elements has been termed ''integration site recycling'' and may serve as a mechanism to protect the host cell genome while allowing Tf2 elements to evolve [23].…”

Section: Author Summarymentioning

confidence: 91%

SREBP Controls Oxygen-Dependent Mobilization of Retrotransposons in Fission Yeast

2005

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Retrotransposons are mobile genetic elements that proliferate through an RNA intermediate. Transposons do not encode transcription factors and thus rely on host factors for mRNA expression and survival. Despite information regarding conditions under which elements are upregulated, much remains to be learned about the regulatory mechanisms or factors controlling retrotransposon expression. Here, we report that low oxygen activates the fission yeast Tf2 family of retrotransposons. Sre1, the yeast ortholog of the mammalian membrane-bound transcription factor sterol regulatory element binding protein (SREBP), directly induces the expression and mobilization of Tf2 retrotransposons under low oxygen. Sre1 binds to DNA sequences in the Tf2 long terminal repeat that functions as an oxygen-dependent promoter. We find that Tf2 solo long terminal repeats throughout the genome direct oxygendependent expression of adjacent coding and noncoding sequences, providing a potential mechanism for the generation of oxygen-dependent gene expression.

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“…Transcription stimulates spontaneous HR (20,46,47,58,69,74,75,78), spontaneous plasmid integration into a chromosome (5), Ty conversion (14,41,44), and gene amplification (40). Transcription also affects gene conversion tract spectra in yeast (77).…”

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confidence: 99%

Transcription of a Donor Enhances Its Use during Double-Strand Break-Induced Gene Conversion in Human Cells

Schildkraut

Miller

Nickoloff

2006

Molecular and Cellular Biology

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Homologous recombination (HR) mediates accurate repair of double-strand breaks (DSBs) but carries the risk of large-scale genetic change, including loss of heterozygosity, deletions, inversions, and translocations. Nearly one-third of the human genome consists of repetitive sequences, and DSB repair by HR often requires choices among several homologous repair templates, including homologous chromosomes, sister chromatids, and linked or unlinked repeats. Donor preference during DSB-induced gene conversion was analyzed by using several HR substrates with three copies of neo targeted to a human chromosome. Repair of I-SceI nucleaseinduced DSBs in one neo (the recipient) required a choice between two donor neo genes. When both donors were downstream, there was no significant bias for proximal or distal donors. When donors flanked the recipient, we observed a marked (85%) preference for the downstream donor. Reversing the HR substrate in the chromosome eliminated this preference, indicating that donor choice is influenced by factors extrinsic to the HR substrate. Prior indirect evidence suggested that transcription might increase donor use. We tested this question directly and found that increased transcription of a donor enhances its use during gene conversion. A preference for transcribed donors would minimize the use of nontranscribed (i.e., pseudogene) templates during repair and thus help maintain genome stability.DNA double-strand breaks (DSBs) are potentially lethal events that can be repaired by homologous recombination (HR) or nonhomologous end-joining (NHEJ). If left unrepaired, DSBs can lead to chromosome loss or cell death. DSBs are caused by ionizing radiation, X-rays, free radicals, chemicals, and nucleases and may occur at stalled replication forks (30). Although DSB repair can be accurate, misrepair can have serious consequences. Genomic rearrangements arising during DSB repair can lead to loss of heterozygosity and, ultimately, carcinogenesis through the activation of proto-oncogenes or inactivation of tumor suppressor genes (4, 45). HR appears to be essential for maintaining genome stability. Cells with defects in HR proteins such as BRCA1/2, XRCC2/3, and other RAD51 paralogs exhibit high levels of genomic instability (6,18,28,42,43,52,68). DSBs are a critical type of DNA damage; unlike single-strand breaks, which have a readily available template for repair, DSB repair by HR requires a search for a homologous template.Repetitive elements make up one-third of the mammalian genome and consist of coding DNA, and noncoding DNA such as satellites that can exist in thousands of copies. Repetitive sequences are scattered throughout the genome, including SINE and LINE elements, and ribosomal RNA gene repeats. HR between linked or unlinked repetitive elements can result in a variety of rearrangements including translocations, duplications, and deletions (45).When DNA is broken, there are many potential homologous sequences that could be used as a repair template, including linked or unlinked repeats, sister...

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Involvement of cDNA in homologous recombination between Ty elements in Saccharomyces cerevisiae.

Cited by 58 publications

References 38 publications

Schizosaccharomyces pombe Retrotransposon Tf2 Mobilizes Primarily through Homologous cDNA Recombination

Schizosaccharomyces pombe Retrotransposon Tf2 Mobilizes Primarily through Homologous cDNA Recombination

SREBP Controls Oxygen-Dependent Mobilization of Retrotransposons in Fission Yeast

Transcription of a Donor Enhances Its Use during Double-Strand Break-Induced Gene Conversion in Human Cells

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