Loss of Expression of the Human MSH3 Gene in Hematological Malignancies

Inokuchi, Koichi; Ikejima, Miyoko; Watanabe, Atsushi; Nakajima, Eiitsu; Orimo, Hideo; Nomura, Takeo; Shimada, Takashi

doi:10.1006/bbrc.1995.2271

Cited by 34 publications

(27 citation statements)

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“…Second, the loss of MSH3 would be expected to have only a small effect on global mismatch repair. Indeed, this appears to be the case both in yeast, where msh3 mutants displayed only a limited dinucleotide repeat instability (13), and in humans, where bone marrow cells from several patients with hematological malignancies could be shown to express extremely low levels of hMSH3 mRNA (14), yet failed to display any phenotype that could be associated with the lack of mismatch repair (T. Shimada and M. Ikejima, personal communication). Third, that MSH6 and MSH3 compete for MSH2 predicts that elevated expression of either protein would result in the ''squelching'' of MSH2 in favor of one or the other heterodimer.…”

mentioning

confidence: 99%

Mismatch repair deficiency associated with overexpression of the MSH3 gene

Marra¹,

Iaccarino²,

Lettieri³

et al. 1998

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

194

166

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We tested the ability of recombinant hMutS␣ (hMSH2͞hMSH6) and hMutS␤ (hMSH2͞hMSH3) heterodimers to complement the mismatch repair defect of HEC59, a human cancer cell line whose extracts lack all three MutS homologues. Although repair of both base͞base mispairs and insertion-deletion loops was restored by hMutS␣, only the latter substrates were addressed in extracts supplemented with hMutS␤. hMutS␣ was also able to complement a defect in the repair of base͞base mispairs in CHO R and HL60R cell extracts. In these cells, methotrexate-induced amplification of the dihydrofolate reductase (DHFR) locus, which also contains the MSH3 gene, led to an overexpression of MSH3 and thus to a dramatic change in the relative levels of MutS␣ and MutS␤. As a rule, MSH2 is primarily complexed with MSH6. MutS␣ is thus relatively abundant in mammalian cell extracts, whereas MutS␤ levels are generally low. In contrast, in cells that overexpress MSH3, the available MSH2 protein is sequestered predominantly into MutS␤. This leads to degradation of the partnerless MSH6 and depletion of MutS␣. CHO R and HL60R cells therefore lack correction of base͞base mispairs, whereas loop repair is maintained by MutS␤. Consequently, frameshift mutations in CHO R are rare, whereas transitions and transversions are acquired at a rate two orders of magnitude above background. Our data thus support and extend the findings of Drummond et al.

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mentioning

confidence: 99%

Mismatch repair deficiency associated with overexpression of the MSH3 gene

Marra¹,

Iaccarino²,

Lettieri³

et al. 1998

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

194

166

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“…Among other proteins, XPB has been isolated from BCR domain and it has been shown that continuous interaction with BCR-ABL provokes XPB deficiency and chromosomal instability (Takeda et al 1999). Finally, hMSH3 Mismatch Repair protein has been found to be reduced in CML patients (Inokuchi et al 1995). However, we can't ignore that the percentage of CML patients with reduced hMSH3 expression in that study was very high (90%), but the number of CML samples examined was small (10).…”

Section: Chronic Myeloid Leukemia (Cml)mentioning

confidence: 77%

DNA Repair Deficiency Associated with Hematological Neoplasms

Economopoulou¹,

Pappa²,

Papageorgiou³

et al. 2011

DNA Repair and Human Health

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“…Such instability syndromes (e.g., xeroderma pigmentosum, ataxia telangiectasia, Bloom syndrome, and Fanconi anemia) show marked predisposition for hematologic malignancies. The expression of the hMSH3 gene, a component of the mismatch repair machinery (40Q, is significantly decreased in patients with hematologic malignancies (41), suggesting a role in leukemogenesis. The role of hMSH3 in radiosensitivity is still unclear; it could be through involvement in transcription-coupled repair of both ultraviolet-and ionizing-radiationinduced DNA damage.…”

Section: Resultsmentioning

confidence: 99%

Risk of childhood leukemia associated with diagnostic irradiation and polymorphisms in DNA repair genes.

Infante‐Rivard

Mathonnet

Sinnett

2000

Environ Health Perspect

114

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The purpose of the study was to measure risk ofchildhood acute lymphoblastic leukemia associated with reported postnatal diagostic X rays and to determine if it was modified in the presence of variants in genes involved i:n DNA repair. We conducted a population-based case-control study with 491 cases and 491 healthy controls among children 0-9 years of age at diagnosis. it is plausible that they would be associated with altered DNA repair capacity and with modified susceptibility to cancer. We can then hypothesize that postnatal irradiation in a child with certain forms of DNA repair genes would be at increased risk of cancer.The objectives of this study were to measure the effect of reported postnatal diagnostic irradiation on childhood acute lymphoblastic leukemia (ALL) and to carry out a preliminary study to assess whether this effect seems modified by DNA repair gene variants. Materials and MethodsGase ascertainment. The

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Loss of Expression of the Human MSH3 Gene in Hematological Malignancies

Cited by 34 publications

References 0 publications

Mismatch repair deficiency associated with overexpression of the MSH3 gene

Mismatch repair deficiency associated with overexpression of the MSH3 gene

DNA Repair Deficiency Associated with Hematological Neoplasms

Risk of childhood leukemia associated with diagnostic irradiation and polymorphisms in DNA repair genes.

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