Flow cytometric analysis of X-ray sensitivity in ataxia telangiectasia

Rudolph, Natalie S.; Latt, Samuel A.

doi:10.1016/0027-5107(89)90104-8

Cited by 64 publications

(27 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, p53 mutations, which confer deficiencies in the G 1 -S checkpoint, are correlated with enhanced spontaneous and UV-stimulated amplification of CAD genes (35,73). Cells cultured from patients with ataxia telangiectasia that are deficient in cell cycle arrest at both the G 1 -S and G 2 -M cell cycle checkpoints (7,49) also exhibit higher frequencies of chromosomal rearrangements, including translocations (37) and deletions (38), and chromosome end-to-end joining (41).…”

mentioning

confidence: 99%

The Saccharomyces cerevisiae RAD9 Checkpoint Reduces the DNA Damage-Associated Stimulation of Directed Translocations

Fasullo

Bennett

AhChing

et al. 1998

Molecular and Cellular Biology

View full text Add to dashboard Cite

Genetic instability in the Saccharomyces cerevisiae rad9 mutant correlates with failure to arrest the cell cycle in response to DNA damage. We quantitated the DNA damage-associated stimulation of directed translocations in RAD9؉ and rad9 mutants. Directed translocations were generated by selecting for His ؉ prototrophs that result from homologous, mitotic recombination between two truncated his3 genes, GAL1::his3-⌬5 and trp1::his3-⌬3::HOcs. Compared to RAD9 ؉ strains, the rad9 mutant exhibits a 5-fold higher rate of spontaneous, mitotic recombination and a greater than 10-fold increase in the number of UV-and X-ray-stimulated His ؉ recombinants that contain translocations. The higher level of recombination in rad9 mutants correlated with the appearance of nonreciprocal translocations and additional karyotypic changes, indicating that genomic instability also occurred among non-his3 sequences. Both enhanced spontaneous recombination and DNA damage-associated recombination are dependent on RAD1, a gene involved in DNA excision repair. The hyperrecombinational phenotype of the rad9 mutant was correlated with a deficiency in cell cycle arrest at the G 2 -M checkpoint by demonstrating that if rad9 mutants were arrested in G 2 before irradiation, the numbers both of UV-and ␥-ray-stimulated recombinants were reduced. The importance of G 2 arrest in DNA damageinduced sister chromatid exchange (SCE) was evident by a 10-fold reduction in HO endonuclease-induced SCE and no detectable X-ray stimulation of SCE in a rad9 mutant. We suggest that one mechanism by which the RAD9-mediated G 2 -M checkpoint may reduce the frequency of DNA damage-induced translocations is by channeling the repair of double-strand breaks into SCE.It has been postulated that DNA damage-induced cell cycle arrest at cell cycle checkpoints maintains genomic stability by allowing time for DNA repair prior to the replication or division of damaged chromatids (67, 68). Consistent with this idea, mutations in genes controlling cell cycle arrest at the G 1 -S checkpoint and G 2 -M checkpoint confer enhanced genetic instability. For example, p53 mutations, which confer deficiencies in the G 1 -S checkpoint, are correlated with enhanced spontaneous and UV-stimulated amplification of CAD genes (35, 73). Cells cultured from patients with ataxia telangiectasia that are deficient in cell cycle arrest at both the G 1 -S and G 2 -M cell cycle checkpoints (7, 49) also exhibit higher frequencies of chromosomal rearrangements, including translocations (37) and deletions (38), and chromosome end-to-end joining (41).In Saccharomyces cerevisiae, DNA-damaging agents stimulate mitotic, homologous recombination and induce cell cycle arrest at cell cycle checkpoints (31, 59). For example, DNA damage-associated recombination between his3 fragments positioned at predetermined loci can result in chromosomal rearrangements, including translocations (18, 19), duplications (16), and deletions (54). HO endonuclease-generated doublestrand breaks (DSBs) stimulate ectopic gene conversi...

show abstract

mentioning

confidence: 99%

The Saccharomyces cerevisiae RAD9 Checkpoint Reduces the DNA Damage-Associated Stimulation of Directed Translocations

Fasullo

Bennett

AhChing

et al. 1998

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…This disorder is characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, chromosomal instability, radiosensitivity, and increased propensity to develop cancer (11). Exposure of A-T cells to ionizing radiation fails to cause initial delays at the G 1 /S and G 2 /M phase transitions (12)(13)(14). These cells exhibit radioresistant DNA synthesis (15)(16), and at longer times postirradiation they are irreversibly delayed in G 2 phase (9,17,18).…”

mentioning

confidence: 99%

Defect in Multiple Cell Cycle Checkpoints in Ataxia-Telangiectasia Postirradiation

Beamish

Williams

Chen

et al. 1996

Journal of Biological Chemistry

129

View full text Add to dashboard Cite

“…Irradiated AT cells also fail to show a normal delay in the transition from G1 to S, again suggesting a defect in a DNA damage-sensitive cell-cycle checkpoint (Friedberg et al 1995). Thus, mutations in the ATM gene appear to void a DNA damage-sensitive checkpoint that prevents cells with damaged chromosomes from entering mitosis (Rudolph and Latt 1989). Indeed, the cellular pathology associated with loss of ATM function suggests a defect in the ability of AT cells to halt their cell cycles in the presence of naturally occurring DNA damage (Murray 1992).…”

mentioning

confidence: 99%

Strange bedfellows in even stranger places: the role of ATM in meiotic cells, lymphocytes, tumors, and its functional links to p53.

Hawley¹,

Friend²

1996

Genes Dev.

View full text Add to dashboard Cite

Flow cytometric analysis of X-ray sensitivity in ataxia telangiectasia

Cited by 64 publications

References 30 publications

The Saccharomyces cerevisiae RAD9 Checkpoint Reduces the DNA Damage-Associated Stimulation of Directed Translocations

The Saccharomyces cerevisiae RAD9 Checkpoint Reduces the DNA Damage-Associated Stimulation of Directed Translocations

Defect in Multiple Cell Cycle Checkpoints in Ataxia-Telangiectasia Postirradiation

Strange bedfellows in even stranger places: the role of ATM in meiotic cells, lymphocytes, tumors, and its functional links to p53.

Contact Info

Product

Resources

About