P VIII.4 Rad9 checkpoint of Saccharomyces cerevisiae suppresses the DNA damage-associated stimulation of directed translocations, depending on the DNA damage agent

Fasullo, Michael; Bennett, T.; Koudelik, J.; AhChing, Peter

doi:10.1016/s0027-5107(97)82787-x

Cited by 11 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a DSB adjacent to only one of the substrates is approximately 10,000-fold less stimulatory for recombination involving both the 300 and 60 bp substrates (Table 1). These results are similar to those of previously published experiments [19,30,31], and suggest that while a DSB adjacent to a single substrate promotes more productive interaction than none at all, DSBs adjacent to both substrates greatly increases productive interaction between them.…”

Section: Dsbs At Both Substrates Greatly Stimulate Recombinationsupporting

confidence: 91%

“…Previous studies have found that an HO endonuclease catalyzed DSB adjacent to one of a pair of recombination substrates in haploid yeast cells is capable of generating translocations at a substantial frequency [31]. Creation of DSBs adjacent to both substrates was shown to further stimulate translocation by HR in both yeast [19] and mammalian cells [32].…”

Section: Discussionmentioning

confidence: 95%

“…Evidence is accumulating that these repeats are involved in the genomic instability associated with some diseases [21,29]. Previous studies have examined HR involving substrates that are similar in size to these repetitive elements and have shown that translocations can occur spontaneously, while DSBs created at one or both substrates greatly increase their frequency [19,30,31,32].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

2008

View full text Add to dashboard Cite

Exposure to ionizing radiation results in a variety of genome rearrangements that have been linked to tumor formation. Many of these rearrangements are thought to arise from the repair of doublestrand breaks (DSBs) by several mechanisms, including homologous recombination (HR) between repetitive sequences dispersed throughout the genome. Doses of radiation sufficient to create DSBs in or near multiple repetitive elements simultaneously could initiate single-strand annealing (SSA), a highly-efficient, though mutagenic, mode of DSB repair. We have investigated the genetic control of the formation of translocations that occur spontaneously and those that form after the generation of DSBs adjacent to homologous sequences on two, non-homologous chromosomes in Saccharomyces cerevisiae. We found that mutations in a variety of DNA repair genes have distinct effects on break-stimulated translocation. Furthermore, the genetic requirements for repair using 300 bp and 60 bp recombination substrates were different, suggesting that the SSA apparatus may be altered in response to changing substrate lengths. Notably, RAD59 was found to play a particularly significant role in recombination between the short substrates that was partially independent of that of RAD52. The high frequency of these events suggests that SSA may be an important mechanism of genome rearrangement following acute radiation exposure.

show abstract

Section: Dsbs At Both Substrates Greatly Stimulate Recombinationsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

2008

View full text Add to dashboard Cite

show abstract

“…We found that at least three forms of genomic instability (chromosome loss, translocation, and BIR) occur after cells have arrested at the checkpoint and subsequently adapted. Previous studies have shown that the rate of nonreciprocal translocation and chromosome loss is higher in checkpoint mutants than in wild-type cells (3,22). Our data address the events which nonetheless appear in wildtype cells and show that these events are preceded by adaptation to a checkpoint arrest.…”

Section: Discussionsupporting

confidence: 59%

Checkpoint Adaptation Precedes Spontaneous and Damage-Induced Genomic Instability in Yeast

Galgoczy

Toczyski

2001

Molecular and Cellular Biology

105

View full text Add to dashboard Cite

Despite the fact that eukaryotic cells enlist checkpoints to block cell cycle progression when their DNA is damaged, cells still undergo frequent genetic rearrangements, both spontaneously and in response to genotoxic agents. We and others have previously characterized a phenomenon (adaptation) in which yeast cells that are arrested at a DNA damage checkpoint eventually override this arrest and reenter the cell cycle, despite the fact that they have not repaired the DNA damage that elicited the arrest. Here, we use mutants that are defective in checkpoint adaptation to show that adaptation is important for achieving the highest possible viability after exposure to DNA-damaging agents, but it also acts as an entrée into some forms of genomic instability. Specifically, the spontaneous and X-ray-induced frequencies of chromosome loss, translocations, and a repair process called break-induced replication occur at significantly reduced rates in adaptation-defective mutants. This indicates that these events occur after a cell has first arrested at the checkpoint and then adapted to that arrest. Because malignant progression frequently involves loss of genes that function in DNA repair, adaptation may promote tumorigenesis by allowing genomic instability to occur in the absence of repair.Cell cycle checkpoints are thought to provide time for DNA repair by delaying cell cycle progress in the face of DNA damage (reviewed in reference 21). Saccharomyces cerevisiae arrests in metaphase for up to 8 h when chromosomes are damaged (e.g., by a double-stranded DNA [dsDNA] break), after which it adapts and continues through the cell cycle (12,18,20). Two classes of proteins have been identified that are required for checkpoint adaptation: repair proteins and signaling proteins. Mutations in KU increase the amount of singlestranded DNA that forms at a dsDNA break, thereby increasing the strength of the checkpoint signal and eliminating adaptation (13). Strains in which the casein kinase II specificity subunits (CKB1 or CKB2) are deleted or that contain a special allele of the gene encoding the polo kinase Cdc5p (cdc5-ad) are also unable to adapt to DNA damage arrest (20).dsDNA breaks can be processed by many mechanisms that result in different outcomes. Archetypal homologous recombination (reattachment of two broken ends using a homologous template) allows error-free repair. However, other, more error-prone outcomes are also seen: (i) nonhomologous end joining results in deletions; (ii) single-strand annealing (SSA) between direct repeats results in deletions; (iii) break-induced replication (BIR) can yield translocations or large gene conversion tracts that cause loss of heterozygosity; (iv) ectopic telomere addition causes terminal truncations; and (v) unrepaired chromosomes may be lost altogether (reviewed in references 4 and 5). Each of these pathways can lead to the loss of genetic information (genomic instability). Which of these scenarios occurs may depend upon where the cell is in the cell cycle when it repairs the damage...

show abstract

“…Interestingly, we observed no significant change in the rate of USCR in the pol3-t mutant (Table 4). While nuclease-catalyzed DSBs can stimulate USCR (Fasullo et al 1998), spontaneous USCR has been proposed to occur by strand invasion and repair synthesis from the sister chromatid subsequent to replicative polymerase pausing (Navarro et al 2007). Gangavarapu et al (2007) have suggested that RAD52-dependent post-replication repair following disruption of lagging strand synthesis may occur by a similar mechanism.…”

Section: Discussionmentioning

confidence: 99%

Mutagenic and Recombinagenic Responses to Defective DNA Polymerase δ Are Facilitated by the Rev1 Protein in pol3-t Mutants of Saccharomyces cerevisiae

et al. 2008

View full text Add to dashboard Cite

Defective DNA replication can result in substantial increases in the level of genome instability. In the yeast Saccharomyces cerevisiae, the pol3-t allele confers a defect in the catalytic subunit of replicative DNA polymerase d that results in increased rates of mutagenesis, recombination, and chromosome loss, perhaps by increasing the rate of replicative polymerase failure. The translesion polymerases Pol h, Pol z, and Rev1 are part of a suite of factors in yeast that can act at sites of replicative polymerase failure. While mutants defective in the translesion polymerases alone displayed few defects, loss of Rev1 was found to suppress the increased rates of spontaneous mutation, recombination, and chromosome loss observed in pol3-t mutants. These results suggest that Rev1 may be involved in facilitating mutagenic and recombinagenic responses to the failure of Pol d. Genome stability, therefore, may reflect a dynamic relationship between primary and auxiliary DNA polymerases.

show abstract

P VIII.4 Rad9 checkpoint of Saccharomyces cerevisiae suppresses the DNA damage-associated stimulation of directed translocations, depending on the DNA damage agent

Cited by 11 publications

References 0 publications

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

Checkpoint Adaptation Precedes Spontaneous and Damage-Induced Genomic Instability in Yeast

Mutagenic and Recombinagenic Responses to Defective DNA Polymerase δ Are Facilitated by the Rev1 Protein in pol3-t Mutants of Saccharomyces cerevisiae

Contact Info

Product

Resources

About