RNase-sensitive DNA modification(s) initiates <i>S. pombe</i> mating-type switching

Vengrova, Sonya; Dalgaard, Jacob Z.

doi:10.1101/gad.289404

Cited by 97 publications

(110 citation statements)

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“…Homothallic fission yeast cells switch their mating type by making use of a site-specific single-stranded lesion that is transformed into a double strand break during the passage of a unidirectional replication fork. This initiates a gene conversion event that replaces the mating type cassette at the active mating type locus (42)(43)(44)(45). Therefore, we analyzed the effect of the absence of H3 Lys-56 acetylation in mating-type switching efficiency in S. pombe.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Histone H3 Lysine 56 Acetylation in Schizosaccharomyces pombe

Xhemalçe

Miller

Driscoll

et al. 2007

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, acetylation of lysine 56 (Lys-56) in the globular domain of histone H3 plays an important role in response to genotoxic agents that interfere with DNA replication. However, the regulation and biological function of this modification are poorly defined in other eukaryotes. Here we show that Lys-56 acetylation in Schizosaccharomyces pombe occurs transiently during passage through S-phase and is normally removed in G 2 . Genotoxic agents that cause DNA double strand breaks during replication elicit a delay in deacetylation of histone H3 Lys-56. In addition, mutant cells that cannot acetylate Lys-56 are acutely sensitive to genotoxic agents that block DNA replication. Moreover, we show that Spbc342.06cp, a previously uncharacterized open reading frame, encodes the functional homolog of S. cerevisiae Rtt109, and that this protein acetylates H3 Lys-56 both in vitro and in vivo. Altogether, our results indicate that both the regulation of histone H3 Lys-56 acetylation by its histone acetyltransferase and histone deacetylase and its role in the DNA damage response are conserved among two distantly related yeast model organisms.Histone acetylation corresponds to the covalent attachment of an acetyl group to a lysine residue. This modification is mediated by histone acetyltransferases (HATs) 7 and is reversible as the acetyl group can be removed through the action of histone deacetylases (HDACs). Lysine acetylation on histones is best characterized for its role in transcriptional regulation, but evidence for a crucial function during replication and DNA damage tolerance is accumulating (1-3). Indeed, newly synthesized histones that are deposited throughout the genome during replication are transiently acetylated at several lysine residues (4, 5). These include sites of acetylation in the N-terminal tails of both histones H3 and H4 (6 -8). Recently, two novel sites of acetylation in the globular domains of newly synthesized histone molecules were uncovered by mass spectrometry of Saccharomyces cerevisiae histones, lysine 91 (Lys-91) of histone H4 (9) and lysine 56 (Lys-56) of histone H3 (10 -15).H3 Lys-56 acetylation (H3 Lys-56-Ac) shows a particular link between DNA replication and DNA damage tolerance. In budding yeast, this modification occurs concomitantly with DNA replication as virtually all the newly synthesized histone H3 molecules deposited throughout the genome are Lys-56-acetylated, whereas in the G 2 /M-phase of the cell cycle the vast majority of H3 Lys-56 is deacetylated (11,(15)(16)(17). However, in response to DNA breaks during replication, histone H3 Lys-56 acetylation is maintained in a DNA damage checkpointdependent manner. In S. cerevisiae this modification plays a key role in surviving DNA damage as cells in which histone H3 cannot be acetylated at Lys-56 are acutely sensitive to genotoxic agents that interfere with DNA replication (10 -13).The deacetylation of H3 Lys-56 requires the Sir2-related HDACs Hst3 and Hst4 (16,17). Hst3 and Hst4 are cell cycles regulated with peak...

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Section: Discussionmentioning

confidence: 99%

Regulation of Histone H3 Lysine 56 Acetylation in Schizosaccharomyces pombe

Xhemalçe

Miller

Driscoll

et al. 2007

Journal of Biological Chemistry

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“…The imprint is a site-and strand-specific moiety, either a nick (Klar 1987;Arcangioli 1998;Kaykov and Arcangioli 2004) or a one-or tworibonucleotide moiety inserted in mat1 gene DNA (Klar 1987;Dalgaard and Klar 1999;Vengrova and Dalgaard 2004). Furthermore, the imprint is installed only during the first-time synthesis of the Watson strand and only when replicated by the lagging-strand DNA replication complex (Singh and Klar 1993;Dalgaard and Klar 1999).…”

Section: Introductionmentioning

confidence: 99%

Unbiased segregation of fission yeast chromosome 2 strands to daughter cells

Klar

Bonaduce

2013

Chromosome Res

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The base complementarity feature (Watson and Crick in Nature 171(4356): [737][738] 1953) and the rule of semi-conservative mode of DNA replication (Messelson and Stahl in Proc Natl Acad Sci U S A 44: [671][672][673][674][675][676][677][678][679][680][681][682] 1958) dictate that two identical replicas of the parental chromosome are produced during replication. In principle, the inherent strand sequence differences could generate nonequivalent daughter chromosome replicas if one of the two strands were epigenetically imprinted during replication to effect silencing/expression of developmentally important genes. Indeed, inheritance of such a strand-and sitespecific imprint confers developmental asymmetry to fission yeast sister cells by a phenomenon called mating/cell-type switching. Curiously, location of DNA strands with respect to each other at the centromere is fixed, and as a result, their selected segregation to specific sister chromatid copies occurs in eukaryotic cells. The yeast system provides a unique opportunity to determine the significance of such biased strand distribution to sister chromatids. We determined whether the cylindrical-shaped yeast cell distributes the specific chromosomal strand to the same cellular pole in successive cycles of cell division. By observing the pattern of recurrent mating-type switching in progenies of individual cells by microscopic analyses, we found that chromosome 2 strands are distributed by the random mode in successive cell divisions. We also exploited unusual "hotspot" recombination features of this system to investigate whether there is selective segregation of strands such that oldest Watsoncontaining strands co-segregate in the diploid cell at mitosis. Our data suggests that chromosome 2 strands are segregated independently to those of the homologous chromosome.

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“…Swi1p and Swi3p likely act at RTS1 to stabilize stalled forks in a manner analogous to their action at the rDNA Ter sites. Forks also pause in a Swi1p-and Swi3p-dependent manner at the site of the imprint (27,29). Imprinting requires in addition the catalytic subunit of DNA polymerase ␣ Swi7p (30), as well as Sap1p, which binds to its cognate site SAS1, located ϳ160 bp from the site of the imprint (31,32).…”

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confidence: 99%