Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations

Robberecht, Caroline; Voet, Thierry; Esteki, Masoud Zamani; Nowakowska, Beata; Vermeesch, Joris Robert

doi:10.1101/gr.145631.112

Cited by 104 publications

(92 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…S2 and S3). Recurrent translocations between paralogous segments of the genome are consistent with rearrangement by nonallelic homologous recombination (NAHR) (25)(26)(27)(28)(29)(30).…”

Section: Genomic Disorder Is Caused By a Recurrent Unbalanced Chromosomementioning

confidence: 89%

Mouse model implicates GNB3 duplication in a childhood obesity syndrome

Goldlust

Hermetz

Catalano

et al. 2013

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

View full text Add to dashboard Cite

Significance We describe a genomic disorder that causes obesity, intellectual disability, and seizures. Children with this syndrome carry an unbalanced chromosome translocation that results in the duplication of over 100 genes, including G protein β3 ( GNB3 ). Although GNB3 polymorphisms have been associated with obesity, hypertension, and diabetes, the mechanism of GNB3 pathogenesis is unknown. We created a transgenic mouse model that carries a duplication of GNB3 , weighs significantly more than wild-type mice, and has excess abdominal fat. GNB3 is highly expressed in the brain and may be important for signaling related to satiety and/or metabolism.

show abstract

“…S2 and S3). Recurrent translocations between paralogous segments of the genome are consistent with rearrangement by nonallelic homologous recombination (NAHR) (25)(26)(27)(28)(29)(30).…”

Section: Genomic Disorder Is Caused By a Recurrent Unbalanced Chromosomementioning

confidence: 89%

Mouse model implicates GNB3 duplication in a childhood obesity syndrome

Goldlust

Hermetz

Catalano

et al. 2013

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

View full text Add to dashboard Cite

show abstract

“…Chromosome rearrangements are important in taxonomic divergence because they affect both genome expression and set up meiotic barriers to interbreeding. In some cases we can link chromosome rearrangements to the presence of mobile elements [250], where they may act either as sources of dispersed homology for recombinational exchange [251] or as active agents of chromosome breakage and rejoining [252,253].…”

Section: Evolutionary Change By Altering Chromosome Composition and Cmentioning

confidence: 99%

How life changes itself: The Read–Write (RW) genome

Shapiro

2013

Physics of Life Reviews

View full text Add to dashboard Cite

The genome has traditionally been treated as a Read-Only Memory (ROM) subject to change by copying errors and accidents. In this review, I propose that we need to change that perspective and understand the genome as an intricately formatted Read-Write (RW) data storage system constantly subject to cellular modifications and inscriptions. Cells operate under changing conditions and are continually modifying themselves by genome inscriptions. These inscriptions occur over three distinct time-scales (cell reproduction, multicellular development and evolutionary change) and involve a variety of different processes at each time scale (forming nucleoprotein complexes, epigenetic formatting and changes in DNA sequence structure). Research dating back to the 1930s has shown that genetic change is the result of cell-mediated processes, not simply accidents or damage to the DNA. This cell-active view of genome change applies to all scales of DNA sequence variation, from point mutations to large-scale genome rearrangements and whole genome duplications (WGDs). This conceptual change to active cell inscriptions controlling RW genome functions has profound implications for all areas of the life sciences.

show abstract

“…Retrotransposons can produce DNA doublestrand breaks, even in the absence of successful retrotransposition (Gasior et al 2006). Some retrotransposons, such as the mammalian L1 element and yeast Ty1 element, are frequently present at sites of chromosome rearrangements and can produce retrotransposed copies of gene transcripts (Derr et al 1991;Esnault et al 2000;Dunham et al 2002;Gilbert et al 2002;Umezu et al 2002;Abeysinghe et al 2003;Maxwell and Curcio 2007;Robberecht et al 2013). Furthermore, mammalian L1 elements and yeast Ty1 elements are both activated by increased reactive oxygen species (ROS) and DNA damage (Rockwood et al 2004;Beauregard et al 2008;Stoycheva et al 2010;Giorgi et al 2011), which are stresses associated with aging (Burhans and Weinberger 2012;Kirkwood and Kowald 2012).…”

mentioning

confidence: 99%

Extension of Saccharomyces paradoxus Chronological Lifespan by Retrotransposons in Certain Media Conditions Is Associated with Changes in Reactive Oxygen Species

VanHoute

Maxwell

2014

Genetics

View full text Add to dashboard Cite

Retrotransposons are mobile DNA elements present throughout eukaryotic genomes that can cause mutations and genome rearrangements when they replicate through reverse transcription. Increased expression and/or mobility of retrotransposons has been correlated with aging in yeast, Caenorhabditis elegans, Drosophila melanogaster, and mammals. The many copies of retrotransposons in humans and various model organisms complicate further pursuit of this relationship. The Saccharomyces cerevisiae Ty1 retrotransposon was introduced into a strain of S. paradoxus that completely lacks retrotransposons to compare chronological lifespans (CLSs) of yeast strains with zero, low, or high Ty1 copy number. Yeast chronological lifespan reflects the progressive loss of cell viability in a nondividing state. Chronological lifespans for the strains were not different in rich medium, but were extended in high Ty1 copy-number strains in synthetic medium and in rich medium containing a low dose of hydroxyurea (HU), an agent that depletes deoxynucleoside triphosphates. Lifespan extension was not strongly correlated with Ty1 mobility or mutation rates for a representative gene. Buffering deoxynucleoside triphosphate levels with threonine supplementation did not substantially affect this lifespan extension, and no substantial differences in cell cycle arrest in the nondividing cells were observed. Lifespan extension was correlated with reduced reactive oxygen species during early stationary phase in high Ty1 copy strains, and antioxidant treatment allowed the zero Ty1 copy strain to live as long as high Ty1 copy-number strains in rich medium with hydroxyurea. This exceptional yeast system has identified an unexpected longevity-promoting role for retrotransposons that may yield novel insights into mechanisms regulating lifespan.

show abstract

Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations

Cited by 104 publications

References 54 publications

Mouse model implicates GNB3 duplication in a childhood obesity syndrome

Mouse model implicates GNB3 duplication in a childhood obesity syndrome

How life changes itself: The Read–Write (RW) genome

Extension of Saccharomyces paradoxus Chronological Lifespan by Retrotransposons in Certain Media Conditions Is Associated with Changes in Reactive Oxygen Species

Contact Info

Product

Resources

About