Ageing and the mismatch repair system

Yehuda, Arie Ben; Globerson, Amiela; Krichevsky, Spencer; On, Hanoch Bar; Kidron, Miriam; Friedlander, Yechiel; Friedman, G.; Yehuda, Dina Ben

doi:10.1016/s0047-6374(00)00208-6

Cited by 51 publications

(30 citation statements)

References 18 publications

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“…It is commonly believed that the rate of microsatellite mutations reflects both the actual rate of occurrence of muta- tions and the efficiency of mismatch repair (30). This has been studied extensively in neoplastic transformation (31) and aging (32). However, we found that one of the more common enzymes involved in DNA repair, MHS2, is expressed by ROP mesangial cells, and in our experience, ROP mice do not develop malignancies at a higher rate.…”

Section: Mesangial Cells With Different D(ca) Repeat Lengthssupporting

confidence: 53%

Glucose Induces Clonal Selection and Reversible Dinucleotide Repeat Expansion in Mesangial Cells Isolated from Glomerulosclerosis-Prone Mice

et al. 2003

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Clonal selection has been proposed as a pathogenetic mechanism in various chronic diseases, such as scleroderma, hypertension, pulmonary fibrosis, interstitial fibrosis of the kidney, atherosclerosis, and uterine leiomyomatosis. We previously found that mesangial cells from ROP mice prone to develop glomerulosclerosis changed their phenotype in response to high glucose concentrations. Here, we investigate whether clonal selection might contribute to this phenotype change. We found that in ROP mice at least two distinct mesangial cell clones exist. They are characterized by a different length of the d(CA) repeat in the MMP-9 promoter and exhibit a significantly different gene expression profile. Exposure of ROP mesangial cells to 25 mmol/l glucose for 35 days induces both clonal selection and reversible dinucleotide repeat expansion. None of these findings were present in mesangial cells isolated from C57BL/6 mice, which are not sclerosis-prone. We conclude that mesangial cell michrochimerism may be a marker for the susceptibility to glomerulosclerosis, that dinucleotide repeat expansion may be a novel mechanism for glucose-induced changes in gene expression, and that clonal selection may partially explain the change in mesangial cell phenotype in diabetes.

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Section: Mesangial Cells With Different D(ca) Repeat Lengthssupporting

confidence: 53%

Glucose Induces Clonal Selection and Reversible Dinucleotide Repeat Expansion in Mesangial Cells Isolated from Glomerulosclerosis-Prone Mice

et al. 2003

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“…Several studies suggest that the capacity for MMR as judged by MSI or mismatch levels is diminished as a function of ageing possibly due to the loss of key MMR proteins (see, e.g. Annett et al, 2005;Ben Yehuda et al, 2000;Krichevsky et al, 2004;Neri et al, 2005). Although we do not know whether correlations between ageing and loss of MMR reflect a direct role for MMR in preventing ageing or are indirect consequences of the ageing process, these studies raise intriguing possibilities.…”

Section: Mmr and Ageingmentioning

confidence: 91%

DNA mismatch repair: Molecular mechanism, cancer, and ageing

Hsieh

Yamane

2008

Mechanisms of Ageing and Development

397

359

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DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.

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“…Many studies have found a significantly higher rate of MSI in older individuals [6,[21][22][23]], but few data suggest a possible cause of the alteration in the MMR system with age, as evidenced by the acquisition of MSI. The age-dependent accumulation of DNA damage seems to affect the frequency of MSI in older individuals [17,22].…”

Section: Journal Of Surgical Oncologymentioning

confidence: 99%