A Unique DNA Recombination Mechanism of the Mating/Cell-type Switching of Fission Yeasts: a Review

Klar, Amar J. S.; Ishikawa, Ken; Moore, Sharon P.

doi:10.1128/microbiolspec.mdna3-0003-2014

Cited by 42 publications

(25 citation statements)

References 73 publications

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“…The heterochromatin domain that silences these cassettes is called the mat2–mat3 region. Lineage-regulated recombination places copies of these transcription-factor-encoding genes into the expression site ( mat1 ), thereby producing a switch in mating type, P to M or M to P 204,205 . In addition to the silencing of mat2 and mat3, H3K9me-heterochromatin has a role in regulating the directionality of this recombination and therefore the pattern of mating-type switching so that P-to-P and M-to-M are disfavoured 205 .…”

Section: Nine: Controlling Cell Differentiationmentioning

confidence: 99%

Ten principles of heterochromatin formation and function

Allshire

Madhani

2017

Nat Rev Mol Cell Biol

597

586

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Heterochromatin is a key architectural feature of eukaryotic chromosomes, which endows particular genomic domains with specific functional properties. The capacity of heterochromatin to restrain the activity of mobile elements, isolate DNA repair in repetitive regions and ensure accurate chromosome segregation is crucial for maintaining genomic stability. Nucleosomes at heterochromatin regions display histone post-translational modifications that contribute to developmental regulation by restricting lineage-specific gene expression. The mechanisms of heterochromatin establishment and of heterochromatin maintenance are separable and involve the ability of sequence-specific factors bound to nascent transcripts to recruit chromatin-modifying enzymes. Heterochromatin can spread along the chromatin from nucleation sites. The propensity of heterochromatin to promote its own spreading and inheritance is counteracted by inhibitory factors. Because of its importance for chromosome function, heterochromatin has key roles in the pathogenesis of various human diseases. In this Review, we discuss conserved principles of heterochromatin formation and function using selected examples from studies of a range of eukaryotes, from yeast to human, with an emphasis on insights obtained from unicellular model organisms.

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Section: Nine: Controlling Cell Differentiationmentioning

confidence: 99%

Ten principles of heterochromatin formation and function

Allshire

Madhani

2017

Nat Rev Mol Cell Biol

597

586

View full text Add to dashboard Cite

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“…However, strategies for elevated rates of genome variation have evolved, some of which are genome-wide, such as in developmental chromosome fragmentation in ciliates [1] and chromosome and gene copy number variation during Leishmania growth [2, 3]. More commonly, enhanced genome change is more localised and caused by deliberate lesion generation, such as during yeast mating type switching, which is induced by HO endonuclease-mediated cleavage in Saccharomyces cerevisiae [4] and locus-directed replication stalling in Schizosaccharomyces pombe [5]. Rearrangements to generate mature receptors and antibodies expressed by T and B cells [6] occur throughout mammalian immune genes and are generated by RAG endonuclease-catalysed DNA breaks [6] or transcription-linked base modification [7].…”

Section: Introductionmentioning

confidence: 99%

Ribonuclease H1-targeted R-loops in surface antigen gene expression sites can direct trypanosome immune evasion

et al. 2018

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Switching of the Variant Surface Glycoprotein (VSG) in Trypanosoma brucei provides a crucial host immune evasion strategy that is catalysed both by transcription and recombination reactions, each operating within specialised telomeric VSG expression sites (ES). VSG switching is likely triggered by events focused on the single actively transcribed ES, from a repertoire of around 15, but the nature of such events is unclear. Here we show that RNA-DNA hybrids, called R-loops, form preferentially within sequences termed the 70 bp repeats in the actively transcribed ES, but spread throughout the active and inactive ES, in the absence of RNase H1, which degrades R-loops. Loss of RNase H1 also leads to increased levels of VSG coat switching and replication-associated genome damage, some of which accumulates within the active ES. This work indicates VSG ES architecture elicits R-loop formation, and that these RNA-DNA hybrids connect T. brucei immune evasion by transcription and recombination.

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“…Homothallic ( h 90 ) colonies sporulate very efficiently because they contain equal proportions of P and M cells due to frequent gene conversions at mat1 . The genetic information at mat1 is replaced with genetic information copied from one of two silent loci, mat2-P or mat3-M [ 2 ]. The organization of the ~35 kb region of chromosome 2 that comprises mat1 , mat2-P and mat3-M in h 90 strains is depicted in Fig 1A .…”

Section: Introductionmentioning

confidence: 99%

New insights into donor directionality of mating-type switching in Schizosaccharomyces pombe

et al. 2018

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Mating-type switching in Schizosaccharomyces pombe entails programmed gene conversion events regulated by DNA replication, heterochromatin, and the HP1-like chromodomain protein Swi6. The whole mechanism remains to be fully understood. Using a gene deletion library, we screened ~ 3400 mutants for defects in the donor selection step where a heterochromatic locus, mat2-P or mat3-M, is chosen to convert the expressed mat1 locus. By measuring the biases in mat1 content that result from faulty directionality, we identified in total 20 factors required for donor selection. Unexpectedly, these included the histone H3 lysine 4 (H3K4) methyltransferase complex subunits Set1, Swd1, Swd2, Swd3, Spf1 and Ash2, the BRE1-like ubiquitin ligase Brl2 and the Elongator complex subunit Elp6. The mutant defects were investigated in strains with reversed donor loci (mat2-M mat3-P) or when the SRE2 and SRE3 recombination enhancers, adjacent to the donors, were deleted or transposed. Mutants in Set1C, Brl2 or Elp6 altered balanced donor usage away from mat2 and the SRE2 enhancer, towards mat3 and the SRE3 enhancer. The defects in these mutants were qualitatively similar to heterochromatin mutants lacking Swi6, the NAD+-dependent histone deacetylase Sir2, or the Clr4, Raf1 or Rik1 subunits of the histone H3 lysine 9 (H3K9) methyltransferase complex, albeit not as extreme. Other mutants showed clonal biases in switching. This was the case for mutants in the NAD+-independent deacetylase complex subunits Clr1, Clr2 and Clr3, the casein kinase CK2 subunit Ckb1, the ubiquitin ligase component Pof3, and the CENP-B homologue Cbp1, as well as for double mutants lacking Swi6 and Brl2, Pof3, or Cbp1. Thus, we propose that Set1C cooperates with Swi6 and heterochromatin to direct donor choice to mat2-P in M cells, perhaps by inhibiting the SRE3 recombination enhancer, and that in the absence of Swi6 other factors are still capable of imposing biases to donor choice.

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A Unique DNA Recombination Mechanism of the Mating/Cell-type Switching of Fission Yeasts: a Review

Cited by 42 publications

References 73 publications

Ten principles of heterochromatin formation and function

Ten principles of heterochromatin formation and function

Ribonuclease H1-targeted R-loops in surface antigen gene expression sites can direct trypanosome immune evasion

New insights into donor directionality of mating-type switching in Schizosaccharomyces pombe

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