Analysis of Gross‐Chromosomal Rearrangements in Saccharomyces cerevisiae

Schmidt, Kristina; Pennaneach, Vincent; Putnam, Christopher D.; Kolodner, Richard D.

doi:10.1016/s0076-6879(05)09027-0

Cited by 52 publications

(69 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because the cells were diploid, they could tolerate a wide assortment of CAs, including large heterozygous deletions. This approach differs from a selection system for elaborating the genetic control of gross chromosomal rearrangements (9), where isolation of CAs relies on selecting events that originate in a small nonessential region of single-copy DNA in the haploid genome.…”

Section: Resultsmentioning

confidence: 99%

Double-strand breaks associated with repetitive DNA can reshape the genome

Argueso

Westmoreland

Mieczkowski

et al. 2008

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

227

222

View full text Add to dashboard Cite

Ionizing radiation is an established source of chromosome aberrations (CAs). Although double-strand breaks (DSBs) are implicated in radiation-induced and other CAs, the underlying mechanisms are poorly understood. Here, we show that, although the vast majority of randomly induced DSBs in G 2 diploid yeast cells are repaired efficiently through homologous recombination (HR) between sister chromatids or homologous chromosomes, Ϸ2% of all DSBs give rise to CAs. Complete molecular analysis of the genome revealed that nearly all of the CAs resulted from HR between nonallelic repetitive elements, primarily Ty retrotransposons. Nonhomologous end-joining (NHEJ) accounted for few, if any, of the CAs. We conclude that only those DSBs that fall at the 3-5% of the genome composed of repetitive DNA elements are efficient at generating rearrangements with dispersed small repeats across the genome, whereas DSBs in unique sequences are confined to recombinational repair between the large regions of homology contained in sister chromatids or homologous chromosomes. Because repeatassociated DSBs can efficiently lead to CAs and reshape the genome, they could be a rich source of evolutionary change.ectopic recombination ͉ gamma radiation ͉ genome rearrangements ͉ nonallelic homologous recombination ͉ retrotransposon

show abstract

Section: Resultsmentioning

confidence: 99%

Double-strand breaks associated with repetitive DNA can reshape the genome

Argueso

Westmoreland

Mieczkowski

et al. 2008

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

227

222

View full text Add to dashboard Cite

show abstract

“…Hom ϩ revertants caused by reversion of a ϩ1 insertion in the HOM3 gene (hom3-10) were selected for on SC-threonine dropout plates. Can r -5FOA r mutants resulting from the loss of the region including CAN1 and URA3 on chromosome V were selected on SC-arginine and uracil dropout plates containing 60 mg/liter canavanine and 1 g/liter 5FOA (5,8).…”

Section: Methodsmentioning

confidence: 99%

“…The median frequency from at least five independent trials is reported. The structure of the GCRs from independent Can r -5FOA r clones was determined as described (8).…”

Section: Methodsmentioning

confidence: 99%

“…Anaerobic suppression represents the fold reduction of mutation rate for a given strain in anaerobic conditions relative to the same strain grown aerobically. dent Can r -5FOA r clones was determined as described (8). Treatment with H 2 O 2 resulted in recovery of translocation, telomere addition, and interstitial deletion classes of GCRs.…”

Section: H2o2 Treatment Increases Genome Rearrangementsmentioning

confidence: 99%

See 1 more Smart Citation

Oxygen metabolism and reactive oxygen species cause chromosomal rearrangements and cell death

Ragu

Faye

Iraqui

et al. 2007

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

Self Cite

View full text Add to dashboard Cite

The absence of Tsa1, a key peroxiredoxin that functions to scavenge H2O2 in Saccharomyces cerevisiae, causes the accumulation of a broad spectrum of mutations including gross chromosomal rearrangements (GCRs). Deletion of TSA1 also causes synthetic lethality in combination with mutations in RAD6 and several key genes involved in DNA double-strand break repair. In the present study we investigated the causes of GCRs and cell death in these mutants. tsa1-associated GCRs were independent of the activity of the translesion DNA polymerases , , and Rev1. Anaerobic growth reduced substantially GCR rates of WT and tsa1 mutants and restored the viability of tsa1 rad6, tsa1 rad51, and tsa1 mre11 double mutants. Anaerobic growth also reduced the GCR rate of rad27, pif1, and rad52 mutants, indicating a role of reactive oxygen species in GCR formation in these mutants. In addition, deletion of TSA1 or H 2O2 treatment of WT cells resulted in increased formation of Rad52 foci, sites of repair of multiple DNA lesions. H 2O2 treatment also induced the GCRs. Our results provide in vivo evidence that oxygen metabolism and reactive oxygen species are important sources of DNA damages that can lead to GCRs and lethal effects in S. cerevisiae.dsDNA break ͉ gross chromosomal rearrangement ͉ translesion DNA synthesis ͉ peroxiredoxin M aintaining genome stability is crucial for cell growth and cell survival. Different genetic disorders, including most human cancers, are associated with different forms of genome instability (1-3). One type of genomic instability observed frequently in many cancers is gross chromosomal rearrangements (GCRs), such as translocations, deletions of chromosome arms, interstitial deletions, inversions, amplifications, chromosome fusions, and aneuploidy. Multiple genes and pathways that suppress GCRs have been characterized by using the yeast Saccharomyces cerevisiae as a model system (4-6). These include genes involved in DNA replication, recombination, and repair, cell-cycle checkpoints that function during DNA replication and repair, and pathways involved in telomere maintenance, chromatin assembly, and detoxification of reactive oxygen species (ROS) (refs. 7 and 8 and references therein). The importance of these pathways for suppressing genome instability is further emphasized by their roles in preventing the development of human cancer (7, 9, 10).Although many pathways that function in the suppression of GCRs have been discovered, little is known about the causes and origin of GCRs. It is generally thought that a major cause of DNA damage that leads to mutations is ROS, which are generated as a normal part of oxygen metabolism but are also produced by ionizing radiation, metabolism of exogenous compounds, and pathological processes such as infection and inflammation (11,12). ROS, such as the superoxide radical, H 2 O 2 , and the hydroxyl radical, can attack almost all cell components and can induce many types of DNA damage, including single-stranded DNA breaks and dsDNA breaks (DSB), base and sugar modificat...

show abstract

“…To study GCR in more tractable way, the chromosome V GCR assay that can detect interstitial deletions or non-reciprocal translocations with micro-homology, non-homology, or divergent homology (referred as homeology) at the rearrangement breakpoint, chromosome fusions as well as deletion of a chromosome arm with addition of a new telomere referred to de novo telomere addition was developed in Saccharomyces cerevisiae [4][5][6]. Studies using this GCR assay have begun to elucidate mechanisms underlying GCR formation [1,5].…”

Section: Introductionmentioning

confidence: 99%

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

et al. 2008

View full text Add to dashboard Cite

Translocations in chromosomes alter genetic information. Although the frequent translocations observed in many tumors suggest the altered genetic information by translocation could promote tumorigenesis, the mechanisms for how translocations are suppressed and produced are poorly understood. The smc6-9 mutation increased the translocation class gross chromosomal rearrangement (GCR). Translocations produced in the smc6-9 strain are unique because they are nonreciprocal and dependent on break-induced replication (BIR) and independent of non-homologous end joining. The high incidence of translocations near repetitive sequences such as δ sequences, ARS, tRNA genes, and telomeres in the smc6-9 strain indicates that Smc5-Smc6 suppresses translocations by reducing DNA damage at repetitive sequences. Synergistic enhancements of translocations in strains defective in DNA damage checkpoints by the smc6-9 mutation without affecting de novo telomere addition class GCR suggest that Smc5-Smc6 defines a new pathway to suppress GCR formation.

show abstract

Analysis of Gross‐Chromosomal Rearrangements in Saccharomyces cerevisiae

Cited by 52 publications

References 12 publications

Double-strand breaks associated with repetitive DNA can reshape the genome

Double-strand breaks associated with repetitive DNA can reshape the genome

Oxygen metabolism and reactive oxygen species cause chromosomal rearrangements and cell death

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

Contact Info

Product

Resources

About