کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10823709 | 1061926 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mismatch repair protein Msh2 contributes to UVB-induced cell cycle arrest in epidermal and cultured mouse keratinocytes
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Nucleotide excision repair (NER), cell cycle regulation and apoptosis are major defence mechanisms against the carcinogenic effects of UVB radiation. NER eliminates UVB-induced DNA photolesions via two subpathways: global genome repair (GGR) and transcription-coupled repair (TCR). In a previous study, we found UVB-induced accumulation of tetraploid (4N) keratinocytes in the epidermis of Xpcâ/â mice (no GGR), but not in Xpaâ/â (no TCR and no GGR) or in wild-type (WT) mice. We inferred that this arrest in Xpcâ/â mice is caused by erroneous replication past photolesions, leading to 'compound lesions' known to be recognised by mismatch repair (MMR). MMR-induced futile cycles of breakage and resynthesis at sites of compound lesions may then sustain a cell cycle arrest. The present experiments with Xpcâ/âMsh2â/â mice and derived keratinocytes show that the MMR protein Msh2 indeed plays a role in the generation of the UVB-induced arrested cells: a Msh2-deficiency lowered significantly the percentage of arrested cells in vivo (40-50%) and in vitro (30-40%). Analysis of calyculin A (CA)-induced premature chromosome condensation (PCC) of cultured Xpcâ/â keratinocytes showed that the delayed arrest occurred in late S phase rather than in G2-phase. Taken together, the results indicate that in mouse epidermis and cultured keratinocytes, the MMR protein Msh2 plays a role in the UVB-induced S-phase arrest. This indicates that MMR plays a role in the UVB-induced S-phase arrest. Alternatively, Msh2 may have a more direct signalling function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 4, Issue 1, 2 January 2005, Pages 81-89
Journal: DNA Repair - Volume 4, Issue 1, 2 January 2005, Pages 81-89
نویسندگان
Marijke van Oosten, Gerdine J Stout, Claude Backendorf, Heggert Rebel, Niels de Wind, Firouz Darroudi, Henk J van Kranen, Frank R de Gruijl, Leon HF Mullenders,