Pedrazzi G, Perrera C, Blaser H, Kuster P, Marra G, Davies S L, Ryu G H, Freire R, Hickson I D, Jiricny J, Stagljar I
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Nucleic Acids Res. 2001 Nov 1;29(21):4378-86. doi: 10.1093/nar/29.21.4378.
Bloom's syndrome (BS) is a rare genetic disorder characterised by genomic instability and cancer susceptibility. BLM, the gene mutated in BS, encodes a member of the RecQ family of DNA helicases. Here, we identify hMLH1, which is involved in mismatch repair (MMR) and recombination, as a protein that directly interacts with BLM both in vivo and in vitro, and that the two proteins co-localise to discrete nuclear foci. The interaction between BLM and hMLH1 appears to have been evolutionarily conserved, as Sgs1p, the Saccharomyces cerevisiae homologue of BLM, interacts with yeast Mlh1p. However, cell extracts derived from BS patients show no obvious defects in MMR compared to wild-type- and BLM-complemented BS cell extracts. We conclude that the hMLH1-BLM interaction is not essential for post-replicative MMR, but, more likely, is required for some aspect of genetic recombination.
布卢姆综合征（BS）是一种罕见的遗传性疾病，其特征为基因组不稳定和易患癌症。BLM是在BS中发生突变的基因，编码DNA解旋酶RecQ家族的一个成员。在此，我们鉴定出参与错配修复（MMR）和重组的hMLH1，它是一种在体内和体外均能直接与BLM相互作用的蛋白质，并且这两种蛋白质共定位于离散的核灶。BLM与hMLH1之间的相互作用似乎在进化上是保守的，因为BLM的酿酒酵母同源物Sgs1p与酵母Mlh1p相互作用。然而，与野生型和BLM互补的BS细胞提取物相比，来自BS患者的细胞提取物在MMR方面没有明显缺陷。我们得出结论，hMLH1-BLM相互作用对于复制后MMR不是必需的，但更可能是基因重组某些方面所必需的。
