To fire or not to fire: origin activation in <i>Saccharomyces cerevisiae</i> ribosomal DNA

Ivessa, Andreas S.; Zakian, Virginia A.

doi:10.1101/gad.1033702

Cited by 23 publications

(14 citation statements)

References 49 publications

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“…Rrm3 helicase has been shown to be a ‘sweepase’ of non-histone protein–DNA complexes, aiding replication of telomeric and subtelomeric DNA (21,61,62). We could not detect differences in the replication profile of the hairpin-forming CGG repeats or quadruplex-forming G 4 T 4 sequences in Rrm3 deficient cells (Figure 5) indicating that this helicase does not affect replication through DNA structures.…”

Section: Resultsmentioning

confidence: 99%

Overcoming natural replication barriers: differential helicase requirements

Anand

Shah

Niu

et al. 2011

Nucleic Acids Research

120

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DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

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Section: Resultsmentioning

confidence: 99%

Overcoming natural replication barriers: differential helicase requirements

Anand

Shah

Niu

et al. 2011

Nucleic Acids Research

120

View full text Add to dashboard Cite

show abstract

“…Rrm3p promotes DNA replication through non-nucleosomal protein–DNA complexes, including the rDNA RFB, Rap1p-binding sites in the telomere, inactive ARS sites, and centromere DNA [101–104]. Rrm3p may act on the same replication intermediates as Dna2p rather than on downstream toxic intermediates formed during repair of faulty replication, since rad51 mutations do not suppress the dna2–2 rrm3 Δ synthetic lethality.…”

Section: Discussionmentioning

confidence: 99%

A Network of Multi-Tasking Proteins at the DNA Replication Fork Preserves Genome Stability

et al. 2005

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To elucidate the network that maintains high fidelity genome replication, we have introduced two conditional mutant alleles of DNA2, an essential DNA replication gene, into each of the approximately 4,700 viable yeast deletion mutants and determined the fitness of the double mutants. Fifty-six DNA2-interacting genes were identified. Clustering analysis of genomic synthetic lethality profiles of each of 43 of the DNA2-interacting genes defines a network (consisting of 322 genes and 876 interactions) whose topology provides clues as to how replication proteins coordinate regulation and repair to protect genome integrity. The results also shed new light on the functions of the query gene DNA2, which, despite many years of study, remain controversial, especially its proposed role in Okazaki fragment processing and the nature of its in vivo substrates. Because of the multifunctional nature of virtually all proteins at the replication fork, the meaning of any single genetic interaction is inherently ambiguous. The multiplexing nature of the current studies, however, combined with follow-up supporting experiments, reveals most if not all of the unique pathways requiring Dna2p. These include not only Okazaki fragment processing and DNA repair but also chromatin dynamics.

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“…2F and 7). In general, spontaneous or MMSinduced damage to replication forks within RDN1 cannot be rescued by convergent replication (32). This is because a major fraction of the RDN1 locus is replicated in a largely unidirectional manner (62).…”

Section: Discussionmentioning

confidence: 99%

Histone H3 Lysine 56 Acetylation and the Response to DNA Replication Fork Damage

Würtele

Kaiser

Bacal

et al. 2012

Molecular and Cellular Biology

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In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) occurs in newly synthesized histones that are deposited throughout the genome during DNA replication. Defects in H3K56ac sensitize cells to genotoxic agents, suggesting that this modification plays an important role in the DNA damage response. However, the links between histone acetylation, the nascent chromatin structure, and the DNA damage response are poorly understood. Here we report that cells devoid of H3K56ac are sensitive to DNA damage sustained during transient exposure to methyl methanesulfonate (MMS) or camptothecin but are only mildly affected by hydroxyurea. We demonstrate that, after exposure to MMS, H3K56ac-deficient cells cannot complete DNA replication and eventually segregate chromosomes with intranuclear foci containing the recombination protein Rad52. In addition, we provide evidence that these phenotypes are not due to defects in base excision repair, defects in DNA damage tolerance, or a lack of Rad51 loading at sites of DNA damage. Our results argue that the acute sensitivity of H3K56ac-deficient cells to MMS and camptothecin stems from a failure to complete the repair of specific types of DNA lesions by recombination and/or from defects in the completion of DNA replication.

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To fire or not to fire: origin activation in Saccharomyces cerevisiae ribosomal DNA

Cited by 23 publications

References 49 publications

Overcoming natural replication barriers: differential helicase requirements

Overcoming natural replication barriers: differential helicase requirements

A Network of Multi-Tasking Proteins at the DNA Replication Fork Preserves Genome Stability

Histone H3 Lysine 56 Acetylation and the Response to DNA Replication Fork Damage

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