MutSbeta exceeds MutSalpha in dinucleotide loop repair.
MutSbeta exceeds MutSalpha in dinucleotide loop repair.
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MutSbeta 在二核苷酸环修复方面超过了 MutSalpha。
DOI：
10.1038/sj.bjc.6605531
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发表时间：
2010-03-16
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
DNA错配识别因子MutSα（MSH 2 + MSH 6）和MutSβ（MSH 2 + MSH 3）的靶底物已被广泛研究。然而，其功能冗余和临床实质的程度仍不清楚。错配修复（MMR）缺陷型肿瘤与微卫星不稳定性（MSI）密切相关，MSI的程度和类型似乎取决于受影响的MMR基因，并与其底物特异性有关。MSH 2和MSH 6的缺乏与单核苷酸和二核苷酸重复不稳定性相关。虽然没有致病性MSH 3突变的报道，它的缺陷也被认为是导致低二核苷酸重复不稳定性。为了评估MutSα和MutSβ的底物特异性和功能性，我们在三种不同的细胞系中使用三种底物构建体、GT错配、1个和2个核苷酸插入/缺失环（IDL）进行了体外MMR试验。我们的研究结果表明，尽管MutSα单独似乎负责GT和IDL 1修复，但MutSα和MutSβ确实在IDL 2修复中具有功能冗余，并且与早期研究相比，MutSβ似乎超过MutSα。这一发现具有临床意义，因为MutSβ在IDL 2修复中的强大作用表明，在低二核苷酸且无单核苷酸重复不稳定性的肿瘤中存在MSH 3缺陷。
The target substrates of DNA mismatch recognising factors MutSα (MSH2+MSH6) and MutSβ (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. To assess the substrate specificities and functionality of MutSα and MutSβ 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. Our results show that though MutSα alone seems to be responsible for GT and IDL1 repair, MutSα and MutSβ indeed have functional redundancy in IDL2 repair and in contrast with earlier studies, MutSβ seems to exceed MutSα. The finding is clinically relevant because the strong role of MutSβ in IDL2 repair indicates MSH3 deficiency in tumours with low dinucleotide and no mononucleotide repeat instability.
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影响因子：
29.4
作者：
Ollila, Saara;Sarantaus, Laura;Nystrom, Minna
通讯作者：
Nystrom, Minna
影响因子：
56.9
作者：
DRUMMOND, JT;LI, GM;MODRICH, P
通讯作者：
MODRICH, P
影响因子：
56.9
作者：
LAHUE, RS;AU, KG;MODRICH, P
通讯作者：
MODRICH, P
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
4
作者：
Wagner, A;Hendriks, Y;Fodde, R
通讯作者：
Fodde, R