| 18567801 | To determine the potential mechanisms of senescence-dependent increases in genomic instability, we analyzed DNA mismatch repair (MMR) efficiency in young and senescent human colonic fibroblast and human embryonic lung fibroblast |
| 18567801 | It was found that MMR activity is significantly reduced in senescent cells |
| 18567801 | Western blot and immunohistochemistry analysis revealed that hMSH2 and MSH6 protein (MutS alpha complex), which is a known key component in the MMR pathway, is markedly down-regulated in senescent cells |
| 18567801 | Moreover, the addition of purified MutS alpha to extracts from senescent cells led to the restoration of MMR activity |
| 18567801 | E2F1 small interfering RNA expression reduced hMSH2 expression and MMR activity in young human primary fibroblast cells |
| 18567801 | Importantly, expression of E2F1 in quiescent cells restored the MSH2 expression as well as MMR activity, whereas E2F1-infected senescent cells exhibited no restoration of MSH2 expression and MMR activity |
| 18567801 | These results indicate that the suppression of E2F1 transcriptional activity in senescent cells lead to stable repression of MSH2, followed by a induction of MutS alpha dysfunction, which results in a reduced cellular MMR capacity in senescent cells |
| 18089797 | Furthermore, v5 was preferentially expressed in mismatch repair (MMR)-deficient cells and tumor tissues, suggesting its role in chromosome stability associated with MMR deficiency |
| 16216462 | This study employed an in vitro model of human CD4+T cell ageing to investigate MMR capacity at various stages of T cell lifespan |
| 16216462 | However, when challenged with supra-physiological levels of DNA mismatches, deficiencies were found in ageing T cell clones in MMR capacity, with the exception of T cell clones from a SENIEUR donor previously shown to maintain effective DNA excision repair |
| 15760303 | Activation of Mrc1, a mediator of the replication checkpoint, by telomere erosion |
| 15760303 | In telomerase-negative cells deleted for RAD9, Mrc1, another checkpoint adaptor previously implicated in the DNA replication checkpoint, mediated Rad53 activation |
| 15760303 | However, unexpectedly, given the formation of an active Rad53-Mrc1 complex in tlc1Delta rad9Delta cells, Mrc1 did not mediate the cell-cycle arrest elicited by telomerase loss |
| 15760303 | Finally, we report that Rad9, Mrc1, Dun1 and Chk1 are activated by phosphorylation after telomerase inactivation |
| 15050284 | We showed significantly higher rates of microsatellite instability (MSI), an indicator of MMR dysfunction in older subjects, compared to young |
| 11479224 | Temozolomide (TMZ) produces O(6)-methylguanine in DNA, which in turn mispairs with thymine, triggering futile DNA mismatch repair (MMR) and ultimately cell death |
| 11479224 | We found previously that in p53-proficient human glioma cells, TMZ-induced futile DNA MMR resulted not in apoptosis but rather in prolonged, p53- and p21-associated G(2)-M arrest and senescence |
| 11479224 | Taken together, these results indicate that Chk1 links TMZ-induced MMR to G(2)-M arrest |
