Abstract:
BACKGROUND:The target substrates of DNA mismatch recognising factors MutSalpha (MSH2+MSH6) and MutSbeta (MSH2+MSH3) have already been widely researched. However, the extent of their functional redundancy and clinical substance remains unclear. Mismatch repair (MMR)-deficient tumours are strongly associated with microsatellite instability (MSI) and the degree and type of MSI seem to be dependent on the MMR gene affected, and is linked to its substrate specificities. Deficiency in MSH2 and MSH6 is associated with both mononucleotide and dinucleotide repeat instability. Although no pathogenic MSH3 mutations have been reported, its deficiency is also suggested to cause low dinucleotide repeat instability. METHODS:To assess the substrate specificities and functionality of MutSalpha and MutSbeta we performed an in vitro MMR assay using three substrate constructs, GT mismatch, 1 and 2 nucleotide insertion/deletion loops (IDLs) in three different cell lines. RESULTS:Our results show that though MutSalpha alone seems to be responsible for GT and IDL1 repair, MutSalpha and MutSbeta indeed have functional redundancy in IDL2 repair and in contrast with earlier studies, MutSbeta seems to exceed MutSalpha. CONCLUSION:The finding is clinically relevant because the strong role of MutSbeta in IDL2 repair indicates MSH3 deficiency in tumours with low dinucleotide and no mononucleotide repeat instability.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Kantelinen J,Kansikas M,Korhonen MK,Ollila S,Heinimann K,Kariola R,Nyström Mdoi
10.1038/sj.bjc.6605531subject
Has Abstractpub_date
2010-03-16 00:00:00pages
1068-73issue
6eissn
0007-0920issn
1532-1827pii
6605531journal_volume
102pub_type
杂志文章abstract::Many theories mention hypersensitive, promiscuous, outlaw or bypass signalling pathways to explain the acquisition of hormone independence in prostate cancer. Hormonal escape of prostate tumours is marked by many biological changes, including mucinous and neuroendocrine differentiation. Since expression of several muc...
journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:2004-02-09 00:00:00
abstract:BACKGROUND:Metastasis is associated with poor prognosis for melanoma. The formation of metastases is a multi-step process, in which cancer cells can subsequently acquire the potential to intravasate into the blood or lymph vessels, disseminate through the circulation, extravasate through the endothelium and invade the ...
journal_title:British journal of cancer
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doi:10.1038/sj.bjc.6606056
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journal_title:British journal of cancer
pub_type: 杂志文章
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journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
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doi:10.1038/sj.bjc.6605650
更新日期:2010-04-27 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.327
更新日期:1994-09-01 00:00:00
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doi:10.1038/sj.bjc.6601124
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pub_type: 杂志文章
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pub_type: 杂志文章,随机对照试验
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.210
更新日期:1994-06-01 00:00:00
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journal_title:British journal of cancer
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:British journal of cancer
pub_type: 杂志文章
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