Altered DNA binding by the human Rad51-R150Q mutant found in breast cancer patients
Altered DNA binding by the human Rad51-R150Q mutant found in breast cancer patients
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DOI：
10.1248/bpb.30.1374
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发表时间：
2007-08-01
影响因子：
2
通讯作者：
Kurumizaka, Hitoshi
中科院分区：
文献类型：
--
作者：
Ishida, Takako;Takizawa, Yoshimasa;Kurumizaka, Hitoshi
人Rad51蛋白（HsRad51）在双链DNA断裂的重组修复过程中催化单链DNA （ssDNA）和双链DNA （dsDNA）之间的同源配对和链交换。在双侧乳腺癌患者中发现了一种HsRad51突变，导致Gin取代Arg150 (R150Q)；然而，这种R150Q突变的后果尚未阐明。为了确定HsRad51（R150Q）突变如何影响HsRad51的功能，在本研究中，我们纯化了HsRad51（R150Q）突变体。纯化后的HsRad51（R150Q）具有完全的atp水解活性。凝胶过滤分析表明，HsRad51（R150Q）也保持了聚合物形成能力。相反，与HsRad51相比，HsRad51（R150Q）的ssDNA和dsdna结合能力明显降低。HsRad51（R150Q）和HsRad51之间dna结合特性的这些差异可能是解释HsRad51（R150Q）突变乳腺癌患者肿瘤发生的重要原因。
The human Rad51 protein (HsRad51) catalyzes homologous pairing and strand exchange between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) during recombinational repair of double-stranded DNA breaks. An HsRad51 mutation that results in the substitution of Gin for Arg150 (R150Q) was found in bilateral breast cancer patients; however, the consequences of this R150Q mutation have not been elucidated. To determine how this HsRad51(R150Q) mutation affects HsRad51 function, in the present study, we purified the HsRad51(R150Q) mutant. The purified HsRad51(R150Q) was completely proficient in the ATP-hydrolyzing activity. A gel filtration analysis revealed that HsRad51(R150Q) also retained the polymer formation ability. In contrast, the ssDNA- and dsDNA-binding abilities of HsRad51(R150Q) were clearly reduced, as compared to those of HsRad51. These differences in the DNA-binding properties between HsRad51(R150Q) and HsRad51 may be important to account for the tumorigenesis in breast cancer patients with the HsRad51(R150Q) mutation.