RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination
RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination
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DOI：
10.1074/jbc.m500265200
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发表时间：
2005-07-29
影响因子：
4.8
通讯作者：
Brosh, RM
中科院分区：
文献类型：
--
作者：
Doherty, KM;Sharma, S;Brosh, RM
理解RecQ解旋酶的分子和细胞功能已经吸引了相当大的兴趣，因为几种以过早衰老和/或癌症为特征的人类疾病已经在遗传上与RecQ家族基因中的突变相关联。虽然人类疾病尚未与RECQ 1中的突变遗传相关，但RecQ解旋酶在维持基因组稳定性方面的突出作用表明RECQ 1解旋酶可能在体内很重要。为了更好地了解RECQ 1的细胞和分子功能，我们研究了它的蛋白质相互作用。使用免疫共沉淀法，我们已经确定了几个DNA修复因子，与RECQ 1在体内。这些修复因子与RECQ 1的直接物理相互作用用纯化的重组蛋白证实。重要的是，RECQ 1刺激人核酸外切酶1的切割活性，错配修复识别复合物MSH 2/6刺激RECQ 1解旋酶活性。这些蛋白质相互作用表明RECQ 1在涉及错配修复因子的途径中的作用。调节基因重组，RecQ解旋酶的建议作用，是支持确定RECQ 1蛋白质的相互作用，并进行了讨论。
Understanding the molecular and cellular functions of RecQ helicases has attracted considerable interest since several human diseases characterized by premature aging and/or cancer have been genetically linked to mutations in genes of the RecQ family. Although a human disease has not yet been genetically linked to a mutation in RECQ1, the prominent roles of RecQ helicases in the maintenance of genome stability suggest that RECQ1 helicase is likely to be important in vivo. To acquire a better understanding of RECQ1 cellular and molecular functions, we have investigated its protein interactions. Using a co-immunoprecipitation approach, we have identified several DNA repair factors that are associated with RECQ1 in vivo. Direct physical interaction of these repair factors with RECQ1 was confirmed with purified recombinant proteins. Importantly, RECQ1 stimulates the incision activity of human exonuclease 1 and the mismatch repair recognition complex MSH2/6 stimulates RECQ1 helicase activity. These protein interactions suggest a role of RECQ1 in a pathway involving mismatch repair factors. Regulation of genetic recombination, a proposed role for RecQ helicases, is supported by the identified RECQ1 protein interactions and is discussed.