A bouquet makes ends meet

Scherthan, Harry

doi:10.1038/35085086

Cited by 377 publications

(378 citation statements)

References 57 publications

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“…This clustering of telomeres is thought to insure proper homolog pairing and synapsis of the homolog axes [60][61][62]. Interestingly both ATM [63] and more recently H2AX [29] have been shown to regulate the persistence of the telomere bouquet.…”

Section: Role Of H2ax In Meiosismentioning

confidence: 99%

H2AX: the histone guardian of the genome

et al. 2004

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At close hand to one's genomic material are the histones that make up the nucleosome. Standing guard, one variant stays hidden doubling as one of the core histones. But, thanks to its prime positioning, a variation in the tail of H2AX enables rapid modification of the histone code in response to DNA damage. A role for H2AX phosphorylation has been demonstrated in DNA repair, cell cycle checkpoints, regulated gene recombination events, and tumor suppression. In this review, we summarize what we have learned about this marker of DNA breaks, and highlight some of the questions that remain to be elucidated about the physiological role of H2AX. We also suggest a model in which chromatin restructuring mediated by H2AX phosphorylation serves to concentrate DNA repair/signaling factors and/or tether DNA ends together, which could explain the pleotropic phenotypes observed in its absence.

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Section: Role Of H2ax In Meiosismentioning

confidence: 99%

H2AX: the histone guardian of the genome

et al. 2004

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“…To determine if such inactivation influences chromosomal recombination, we examined telomere clustering, synaptonemal complexes, sex bodies and chiasmata frequency in meiocytes of mTert null and control mice according to the standard procedure . It has been suggested that meiotic telomere clustering might support the alignment of homologs prior to their synaptic pairing (Scherthan 2001). We found no difference in the bouquet formation between the spermatocytes of mTert null and control mice (data not shown).…”

Section: Htert Expression Influences Telomere-nuclear Matrix Associationmentioning

confidence: 99%

hTERT associates with human telomeres and enhances genomic stability and DNA repair

et al. 2003

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Ectopic expression of telomerase in telomerase-silent cells is sufficient to overcome senescence and to extend cellular lifespan. We show here that the catalytic subunit of human telomerase (hTERT) crosslinks telomeres. This interaction is blocked by the telomere repeat binding factor 1, but not by a dominant negative form of this protein. It is also abolished by destruction of the RNA component of telomerase as well as by mutations in the hTERT protein.Ectopic expression of hTERT leads to transcriptional alterations of a subset of genes and changes in the interaction of the telomeres with the nuclear matrix. This is associated with reduction of spontaneous chromosome damage in G 1 cells, enhancement of the kinetics of DNA repair and an increase in NTP levels. The effect on DNA repair is likely indirect as TERT does not directly affect DNA end rejoining in vitro or meiotic recombination in vivo. The observed effects of hTERT occurred rapidly before any significant lengthening of telomeres was observed. Our findings establish an intimate relationship between hTERT-telomere interactions and alteration in transcription of a subset of genes that may lead to increased genomic stability and enhanced repair of genetic damage. These novel functions of telomerase are distinct from its known effect on telomere length and have potentially important biological consequences.

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“…These mechanisms of homolog association include DSB-independent pairing, meiotic recombination, synaptonemal complex formation, meiotic telomere reorganization, and an achiasmate segregation system (for review, see Roeder 1997;Kleckner 1998, 1999;Scherthan 2001;Burgess 2002;Kemp et al 2004). Elucidation of the relative contributions and interplay of these processes to accurate chromosome pairing and segregation has aided understanding of homolog associations in budding yeast.…”

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confidence: 99%

Multiple branches of the meiotic recombination pathway contribute independently to homolog pairing and stable juxtaposition during meiosis in budding yeast

Peoples-Holst

Burgess

2005

Genes Dev.

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A unique aspect of meiosis is the segregation of homologous chromosomes at the meiosis I division. Homologs are physically connected prior to segregation by crossing over between nonsister chromatids. Crossovers arise from the repair of induced double-strand breaks (DSBs). In many organisms, more DSBs are formed than crossovers in a given nucleus. It has been previously suggested that repair of DSBs to noncrossover recombination products aids homolog alignment. Here we explore how two modes of the meiotic recombination pathway (crossover and noncrossover) and meiotic telomere reorganization contribute to the pairing and close juxtaposition of homologous chromosomes in budding yeast. We found that intermediates in the DSB repair pathway leading to both crossover and noncrossover recombination products contribute independently to close, stable homolog juxtaposition (CSHJ), a measurable state of homolog pairing. Analysis of the ndj1⌬ mutant indicates that the effect of meiotic telomere reorganization on CSHJ is exerted through recombination intermediates at interstitial chromosomal loci, perhaps through the noncrossover branch of the DSB repair pathway. We suggest that transient, early DSB-initiated interactions, including those that give rise to noncrossovers, are important for homolog recognition and juxtaposition.[Keywords: Homolog; meiosis; pairing; recombination; telomeres]Received December 28, 2004; revised version accepted February 15, 2005. Meiosis is the process in which a parent diploid cell undergoes two rounds of chromosome segregation, after one round of replication, to yield four haploid gametes. A universal component of meiosis I is the reductional segregation of homologous chromosomes. Nondisjunction, or improper segregation of homologs, at this stage can lead to gamete aneuploidy. Three factors contribute to the tension required for the reductional segregation of homologs at anaphase I in most organisms: (1) crossing over between homologous chromosomes, (2) cohesion between sister chromatids, and (3) monopolar spindle attachment of sister chromatids at metaphase (Page and Hawley 2003).Crossing over involves the reciprocal exchange of chromosome arms and can be visualized at late stages of meiotic prophase as chiasmata. Such exchange events are a manifestation of double-strand break (DSB)-promoted homologous recombination. Formation and repair of meiotically induced DSBs involve both DSB repair enzymes and meiosis-specific factors (for reviews, see Zickler and Kleckner 1999;Keeney 2001). Meiosis-specific factors bias recombination between homologous chromosomes instead of sister chromatids (Schwacha and Kleckner 1997) and ensure that at least one crossover occurs between every homolog pair (for review, see Bishop and Zickler 2004).A key event in crossover formation is the recognition and pairing of homologous chromosomes. An outstanding question is what brings homologs together in meiosis. Is it early molecular events, late-forming molecules in which homologs are clearly linked by chemical or hyd...

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A bouquet makes ends meet

Abstract: The 'chromosomal bouquet' is a polarized chromosomal arrangement that is highly conserved among eukaryotes. There have been many hypotheses about its role in the pairing of meiotic chromosomes, but until recently these have been difficult to test.

Cited by 377 publications

References 57 publications

H2AX: the histone guardian of the genome

H2AX: the histone guardian of the genome

hTERT associates with human telomeres and enhances genomic stability and DNA repair

Multiple branches of the meiotic recombination pathway contribute independently to homolog pairing and stable juxtaposition during meiosis in budding yeast

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