Are all repeats created equal? Understanding DNA repeats at an individual level

Yang, Jinpu; Li, Fēi

doi:10.1007/s00294-016-0619-x

Cited by 16 publications

(18 citation statements)

References 56 publications

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“…Repetitive DNA sequences are highly prone to DNA DSBs and may be hotspots for meiotic crossover and other recombination events, some of which can cause genome instability [ 18 ]. Recombination between repetitive DNA sequences frequently results in chromosome rearrangements, a hallmark of cancer and hereditary disorders [ 17 , 19 ]. In this regard, heterochromatin formation at repetitive elements is a protective mechanism evolved for suppressing aberrant recombination events by prohibiting illegitimate recombination between dispersed repetitive DNA elements [ 17 ].…”

Section: Genomic Instability In Heterochromatic Repetitive Dna Seqmentioning

confidence: 99%

Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair

Nair

Shoaib

Sørensen

2017

IJMS

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Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage.

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Section: Genomic Instability In Heterochromatic Repetitive Dna Seqmentioning

confidence: 99%

Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair

Nair

Shoaib

Sørensen

2017

IJMS

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“…It is tempting to speculate that such interactions are not restricted to RIP (and MIP) and may underlie a variety of chromosomal phenomena that sport recombination-independent pairing and (epi)genetic modification of homologous DNA sequences. Given the emerging higher-order structures of copious repetitive DNA present at (peri)centromeric and (sub)telomeric regions of eukaryotic chromosomes (e.g., Yang and Li 2016), it is not impossible to envision that homologous dsDNA/dsDNA interactions might also be particularly important in this broader context.…”

Section: Models Of Direct Dsdna/dsdna Interactionsmentioning

confidence: 99%

Recombination-independent recognition of DNA homology for repeat-induced point mutation

Gladyshev

Kleckner

2016

Curr Genet

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Numerous cytogenetic observations have shown that homologous chromosomes (or individual chromosomal loci) can engage in specific pairing interactions in the apparent absence of DNA breakage and recombination, suggesting that canonical recombination-mediated mechanisms may not be the only option for sensing DNA/DNA homology. One proposed mechanism for such recombination-independent homology recognition involves direct contacts between intact double-stranded DNA molecules. The strongest in vivo evidence for the existence of such a mechanism is provided by the phenomena of homology-directed DNA modifications in fungi, known as repeat-induced point mutation (RIP, discovered in Neurospora crassa) and methylation-induced premeiotically (MIP, discovered in Ascobolus immersus). In principle, Neurospora RIP can detect the presence of gene-sized DNA duplications irrespectively of their origin, underlying nucleotide sequence, coding capacity or relative, as well as absolute positions in the genome. Once detected, both sequence copies are altered by numerous cytosine-to-thymine (C-to-T) mutations that extend specifically over the duplicated region. We have recently shown that Neurospora RIP does not require MEI-3, the only RecA/Rad51 protein in this organism, consistent with a recombination-independent mechanism. Using an ultra-sensitive assay for RIP mutation, we have defined additional features of this process. We have shown that RIP can detect short islands of homology of only three base-pairs as long as many such islands are arrayed with a periodicity of 11 or 12 base-pairs along a pair of DNA molecules. While the presence of perfect homology is advantageous, it is not required: chromosomal segments with overall sequence identity of only 35–36 % can still be recognized by RIP. Importantly, in order for this process to work efficiently, participating DNA molecules must be able to co-align along their lengths. Based on these findings, we have proposed a model, in which sequence homology is detected by direct interactions between slightly-extended double-stranded DNAs. As a next step, it will be important to determine if the uncovered principles also apply to other processes that involve recombination-independent interactions between homologous chromosomal loci in vivo as well as to protein-free DNA/DNA interactions that were recently observed under biologically relevant conditions in vitro.

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“…Fission yeast (Schizosaccharomyces pombe) has emerged as an excellent model for studying heterochromatin. Heterochromatin in fission yeast comprises peri-centromeres, telomere, and mating-type regions (6,7). As in multicellular organisms, H3K9 methylation and hypoacetylation are enriched in heterochromatin in fission yeast.…”

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confidence: 99%

Coordinated regulation of heterochromatin inheritance by Dpb3–Dpb4 complex

Dong

et al. 2017

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

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During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the inheritance of H3K9 methylation during DNA replication depends on the catalytic subunit of DNA polymerase epsilon, Cdc20. Here we show that the histone-fold subunit of Pol epsilon, Dpb4, interacts an uncharacterized small histone-fold protein, SPCC16C4.22, to form a heterodimer in fission yeast. We demonstrate that SPCC16C4.22 is nonessential for viability and corresponds to the true ortholog of Dpb3. We further show that the Dpb3-Dpb4 dimer associates with histone deacetylases, chromatin remodelers, and histones and plays a crucial role in the inheritance of histone hypoacetylation in heterochromatin. We solve the 1.9-Å crystal structure of Dpb3-Dpb4 and reveal that they form the H2A-H2B-like dimer. Disruption of Dpb3-Dpb4 dimerization results in loss of heterochromatin silencing. Our findings reveal a link between histone deacetylation and H3K9 methylation and suggest a mechanism for how two processes are coordinated during replication. We propose that the Dpb3-Dpb4 heterodimer together with Cdc20 serves as a platform for the recruitment of chromatin modifiers and remodelers that mediate heterochromatin assembly during DNA replication, and ensure the faithful inheritance of epigenetic marks in heterochromatin.

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Are all repeats created equal? Understanding DNA repeats at an individual level

Cited by 16 publications

References 56 publications

Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair

Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair

Recombination-independent recognition of DNA homology for repeat-induced point mutation

Coordinated regulation of heterochromatin inheritance by Dpb3–Dpb4 complex

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