Communication between homologous chromosomes: genetic alterations at a nuclease‐hypersensitive site can alter mitotic chromatin structure at that site both in cis and in trans

Keeney, Scott; Kleckner, Nancy

doi:10.1046/j.1365-2443.1996.d01-257.x

Cited by 71 publications

(52 citation statements)

References 38 publications

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“…McClintock (11), in which the author states that ''there is a tendency for chromosomes to associate 2-by-2 in the prophase of meiosis'']. For example, Henikoff proposed the existence of some form of communication between homologous DNA sequences outside of the recombination process (12) and Keeney and Kleckner (13) hypothesized that ''homology is sensed directly at the DNA level, guided by direct physical interactions between DNA duplexes in accessible regions . .…”

Section: Homology Recognition Enigmamentioning

confidence: 99%

The homology recognition well as an innate property of DNA structure

Kornyshev

Wynveen

2009

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

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Mutual recognition of homologous sequences of DNA before strand exchange is considered to be the most puzzling stage of recombination of genes. In 2001, a mechanism was suggested for a doublestranded DNA molecule to recognize from a distance its homologous match in electrolytic solution without unzipping [Kornyshev AA, Leikin S (2001) Phys Rev Lett 86:3666 -3669]. Based on a theory of electrostatic interactions between helical molecules, the difference in the electrostatic interaction energy between homologous duplexes and between nonhomologous duplexes, called the recognition energy, was calculated. Here, we report a theoretical investigation of the form of the potential well that DNA molecules may feel sliding along each other. This well, the bottom of which is determined by the recognition energy, leads to trapping of the molecular tracks of the same homology in direct juxtaposition. A simple formula for the shape of the well is obtained. The well is quasi-exponential. Its half-width is determined by the helical coherence length, introduced first in the same 2001 article, the value of which, as the latest study shows, is Ϸ10 nm.Decades of research into homologous recombination have unraveled many of the details concerning the transfer of information between 2 homologous sequences. By contrast, the processes by which the interacting molecules initially colocalize are largely unknown. How can 2 homologous needles find each other in the genomic haystack?- Barzel and Kupiec (2008) R ecombination of genes is a process in which sequences are exchanged between 2 DNA molecules. In homologous recombination fragments of the same homology, those that have almost identical sequences are swapped. This makes possible gene shuffling between 2 parental copies of DNA, crucial for evolution and genetic diversity. A similar process is used in DNA repair, when the cell uses a backup copy of the genome as a template for repairs. It is generally accepted that understanding recombination of genes is one of the key challenges of the ''postgenomic era'' (1). Homology Recognition EnigmaThe key point in homologous recombination is the swapping of correct genes: only regions with homologous sequences should be exchanged or used as a template for repair. Recombination mistakes are known to cause a variety of severe genetic diseases (2, 3) and contribute to aging (4). Fortunately, such errors are rare. The recognition of sequence homology occurs with amazing precision. In site-specific recombination, the exchange happens at specific, designated loci recognized by the complex recombination machinery of the cell (involving multiple proteins). In homologous recombination the exchange can occur anywhere. It was established that at least 50-to 100-bp homology is required for it (see, e.g., refs. 5-7). This ensures that the fragments belong to 2 alleles of the same gene rather than to different genes. The long-range goal is an in-depth understanding of the recognition mechanism to be able to develop procedures that could further minimize these ...

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Section: Homology Recognition Enigmamentioning

confidence: 99%

The homology recognition well as an innate property of DNA structure

Kornyshev

Wynveen

2009

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

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“…There are several lines of evidence that the frequency of DSBs is regulated by elements of chromatin structure rather than primary DNA sequence (2). First, recombination hotspots exhibit hypersensitivity to nucleases (6)(7)(8)(9)(10). Some loci (8,9) undergo meiosis-specific alterations in nuclease sensitivity prior to DSB formation, although no such changes are observed at other loci (6).…”

Section: Introductionmentioning

confidence: 99%

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae

et al. 2008

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The rate of meiotic recombination in the yeast Saccharomyces cerevisiae varies widely in different regions of the genome with some genes having very high levels of recombination (hotspots). A variety of experiments done in yeast suggest that hotspots are a feature of chromatin structure rather than a feature of primary DNA sequence. We examined the effects of mutating a variety of enzymes that affect chromatin structure on the recombination activity of the well-characterized HIS4 hotspot including the Set2p and Dot1p histone methylases, the Hda1p and Rpd3p histone deacetylases, the Sin4p global transcription regulator, and a deletion of one of the two copies of the genes encoding histone H3-H4. Loss of Set2p or Rpd3p substantially elevated HIS4 hotspot activity, and loss of Hda1p had a smaller stimulatory effect; none of the other alterations had a significant effect. The increase of HIS4 hotspot activity in set2 and rpd3 strains is likely to be related to the recent finding that histone H3 methylation by Set2p directs deacetylation of histones by Rpd3p. IntroductionThe rate of meiotic recombination varies considerably at different positions in the yeast genome (1,2). This variation reflects differences in the frequency of local meiosis-specific doublestrand DNA breaks (DSBs), the recombination-initiating lesion (3,4) catalyzed by Spo11p and associated proteins (5). There are several lines of evidence that the frequency of DSBs is regulated by elements of chromatin structure rather than primary DNA sequence (2). First, recombination hotspots exhibit hypersensitivity to nucleases (6-10). Some loci (8,9) undergo meiosis-specific alterations in nuclease sensitivity prior to DSB formation, although no such changes are observed at other loci (6). Since all nuclease-hypersensitive regions are not meiotic Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Conflicts of interest None. NIH Public AccessAuthor Manuscript DNA Repair (Amst) (6,10), "open" chromatin appears necessary, but not sufficient, for meiotic recombination hotspot activity. Second, insertion of a nucleosome-excluding sequence into the yeast genome creates a recombination hotspot (11). Third, the activity of some hotspots requires the binding of transcription factors, but not high levels of transcription (2). This result has been interpreted as indicating that chromatin modifications associated with transcription factor binding stimulate both transcription and recombination. Finally, some mutants that affect chromatin modifications reduce the frequency of meiosis-specific DSBs. In the yeast S. pombe, mutatio...

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“…Homologous pairing was also observed in diploid budding yeast during vegetative growth, although the extent of the pairing is controversial among literature (12)(13)(14)(15). Unlike the Drosophila homologous chromosomes that stably associate with each other, the yeast chromosomes tend to interact more dynamic and sporadic at interstitial locations (12,14).…”

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confidence: 99%

Interallelic interaction and gene regulation in budding yeast

Zhang

Bai

2016

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

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In Drosophila, homologous chromosome pairing leads to "transvection," in which the enhancer of a gene can regulate the allelic transcription in trans. Interallelic interactions were also observed in vegetative diploid budding yeast, but their functional significance is unknown. Here, we show that a GAL1 reporter can interact with its homologous allele and affect its expression. By ectopically inserting two allelic reporters, one driven by wild-type GAL1 promoter (WT GAL1pr) and the other by a mutant promoter with delayed response to galactose induction, we found that the two reporters physically associate, and the WT GAL1pr triggers synchronized firing of the defective promoter and accelerates its activation without affecting its steady-state expression level. This interaction and the transregulatory effect disappear when the same reporters are located at nonallelic sites. We further demonstrated that the activator Gal4 is essential for the interallelic interaction, and the transregulation requires fully activated WT GAL1pr transcription. The mechanism of this phenomenon was further discussed. Taken together, our data revealed the existence of interallelic gene regulation in yeast, which serves as a starting point for understanding long-distance gene regulation in this genetically tractable system. homologous pairing | interallelic interaction | interallelic regulation | transvection | single-cell gene expression

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Communication between homologous chromosomes: genetic alterations at a nuclease‐hypersensitive site can alter mitotic chromatin structure at that site both in cis and in trans

Cited by 71 publications

References 38 publications

The homology recognition well as an innate property of DNA structure

The homology recognition well as an innate property of DNA structure

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae

Interallelic interaction and gene regulation in budding yeast

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