Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice

Treuner, Kai; Helton, Rob; Barlow, Carrolee

doi:10.1038/sj.onc.1207604

Cited by 35 publications

(29 citation statements)

References 27 publications

(33 reference statements)

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“…Until the present study, increased retroviral infection was, in fact, the only major phenotype described for a RAD52 deficiency in vertebrate cells. It is also worth mentioning that loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice, possibly by suppressing excessive recombination (Treuner et al, 2004). Although the precise role of Rad52 in this rescue is currently unclear, this finding further supports an important in vivo function of Rad52 in vertebrates.…”

Section: Possible Roles Of Vertebrate Rad52 In Repairmentioning

confidence: 61%

Evidence for a Role of Vertebrate Rad52 in the Repair of Topoisomerase II–Mediated DNA Damage

Adachi

Iiizumi

Koyama

2005

DNA and Cell Biology

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DNA topoisomerase II (Top2) inhibitors are useful as anticancer agents, mostly by virtue of their ability to induce DNA double-strand breaks (DSBs). These DSBs are repaired almost exclusively by Rad52-dependent homologous recombination (HR) in yeast. However, we have recently shown that in vertebrate cells such lesions are primarily repaired by nonhomologous end-joining, but not HR. This finding, taken together with previous observations that disruption of RAD52 does not severely affect HR in vertebrate cells, makes it highly unlikely that Rad52 contributes to the repair of Top2-mediated DNA damage. However, in this paper we show that chicken cells lacking Rad52 do exhibit increased sensitivity to the Top2 inhibitor VP-16. Remarkably, the level of hypersensitivity of RAD52-null cells was comparable to that of RAD54-null cells, albeit only at high doses. Our data thus provide the first demonstration of a major repair defect associated with loss of Rad52 in vertebrate cells.

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Section: Possible Roles Of Vertebrate Rad52 In Repairmentioning

confidence: 61%

Evidence for a Role of Vertebrate Rad52 in the Repair of Topoisomerase II–Mediated DNA Damage

Adachi

Iiizumi

Koyama

2005

DNA and Cell Biology

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“…This long-term study was complicated by the fact that AtmϪ/Ϫ mice develop aggressive TCLs. Virtually all AtmϪ/Ϫ mice succumb to aggressive TCLs, ultimately leading to death (4,21). The ongoing loss of animals to TCLs precluded performing OGTTs on predetermined groups.…”

Section: Resultsmentioning

confidence: 99%

Impaired insulin secretion in a mouse model of ataxia telangiectasia

Miles

Treuner²,

Latronica³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Lymphomas developed in Atm/ Rag-1 or Atm/Rag-2 double mutant mice, however, did contain different types of translocations, leading to the hypothesis that translocations and other chromosome aberrations derived from aberrant responses to DSBs are the major mechanisms of ATM deficiency-associated lymphomagenesis (30,31). Inactivation of Rad52 also increased lymphoma latency in Atmdeficient mice, suggesting the involvement of homologous recombination in creating such translocations (40). The recent identification of the Drosophila ortholog of the human HEL308 (a POLQ paralog) as mus301/spn-C, which is involved in repair of meiotic DSBs and meiotic checkpoint activation (19), suggests potential involvement of POLQ in homologous recombination.…”

Section: Discussionmentioning

confidence: 99%

The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm

Shima

Munroe

Schimenti

2004

Molecular and Cellular Biology

129

160

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chaos1 (for chromosome aberrations occurring spontaneously 1) is a recessive mutation that was originally identified in a phenotype-based screen for chromosome instability mutants in mice. Mutant animals exhibit significantly higher frequencies of spontaneous and radiation-or mitomycin C-induced micronucleated erythrocytes, indicating a potential defect in homologous recombination or interstrand cross-link repair. The chaos1 allele was genetically associated with a missense mutation in Polq, which encodes DNA polymerase . We demonstrate here that chaos1 is a mutant allele of Polq by using two genetic approaches: chaos1 mutant phenotype correction by a bacterial artificial chromosome carrying wild-type Polq and a failed complementation test between chaos1 and a Polq-disrupted allele generated by gene targeting. To investigate the potential involvement of Polq in DNA double-strand break repair, we introduced chaos1 into an Atm (for ataxia telangiectasia mutated)-deficient background. The majority (ϳ90%) of double-homozygous mice died during the neonatal period. Surviving double mutants exhibited synergistic phenotypes such as severe growth retardation and enhanced chromosome instability. However, remarkably, double mutants had delayed onset of thymic lymphoma, significantly increasing life span. These data suggest a unique role of Polq in maintaining genomic integrity, which is probably distinctive from the major homologous recombination pathway regulated by ATM.

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Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice

Cited by 35 publications

References 27 publications

Evidence for a Role of Vertebrate Rad52 in the Repair of Topoisomerase II–Mediated DNA Damage

Evidence for a Role of Vertebrate Rad52 in the Repair of Topoisomerase II–Mediated DNA Damage

Impaired insulin secretion in a mouse model of ataxia telangiectasia

The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm

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