Bachrati Csanád Z, Borts Rhona H, Hickson Ian D
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Nucleic Acids Res. 2006 May 2;34(8):2269-79. doi: 10.1093/nar/gkl258. Print 2006.
The Bloom's syndrome helicase, BLM, is a member of the highly conserved RecQ family, and possesses both DNA unwinding and DNA strand annealing activities. BLM also promotes branch migration of Holliday junctions. One role for BLM is to act in conjunction with topoisomerase IIIalpha to process homologous recombination (HR) intermediates containing a double Holliday junction by a process termed dissolution. However, several lines of evidence suggest that BLM may also act early in one or more of the recombination pathways to eliminate illegitimate or aberrantly paired DNA joint molecules. We have investigated whether BLM can disrupt DNA displacement loops (D-loops), which represent the initial strand invasion step of HR. We show that mobile D-loops created by the RecA recombinase are a highly preferred substrate for BLM with the invading strand being displaced from the duplex. We have identified structural features of the D-loop that determine the efficiency with which BLM promotes D-loop dissociation. We discuss these results in the context of models for the role of BLM as an 'anti-recombinase'.
布卢姆综合征解旋酶BLM是高度保守的RecQ家族成员,具有DNA解旋和DNA链退火活性。BLM还能促进霍利迪连接体的分支迁移。BLM的一个作用是与拓扑异构酶IIIα协同作用,通过一种称为溶解的过程处理含有双霍利迪连接体的同源重组(HR)中间体。然而,几条证据表明,BLM也可能在一种或多种重组途径的早期发挥作用,以消除非法或异常配对的DNA连接分子。我们研究了BLM是否能破坏DNA置换环(D环),D环代表HR的初始链侵入步骤。我们发现,由RecA重组酶产生的移动D环是BLM的高度优选底物,侵入链从双链体中被置换出来。我们已经确定了D环的结构特征,这些特征决定了BLM促进D环解离的效率。我们在BLM作为“抗重组酶”作用的模型背景下讨论了这些结果。