Takeda N, Shibuya M, Maru Y
Department of Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan.
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):203-7. doi: 10.1073/pnas.96.1.203.
The previously uncharacterized CDC24 homology domain of BCR, which is missing in the P185 BCR-ABL oncogene of Philadelphia chromosome (Ph1)-positive acute lymphocytic leukemia but is retained in P210 BCR-ABL of chronic myelogeneous leukemia, was found to bind to the xeroderma pigmentosum group B protein (XPB). The binding appeared to be required for XPB to be tyrosine-phosphorylated by BCR-ABL. The interaction not only reduced both the ATPase and the helicase activities of XPB purified in the baculovirus system but also impaired XPB-mediated cross-complementation of the repair deficiency in rodent UV-sensitive mutants of group 3. The persistent dysfunction of XPB may in part underlie genomic instability in blastic crisis.
在费城染色体（Ph1）阳性急性淋巴细胞白血病的P185 BCR-ABL癌基因中缺失但在慢性粒细胞白血病的P210 BCR-ABL中保留的BCR的先前未被表征的CDC24同源结构域，被发现与着色性干皮病B组蛋白（XPB）结合。这种结合似乎是XPB被BCR-ABL酪氨酸磷酸化所必需的。这种相互作用不仅降低了在杆状病毒系统中纯化的XPB的ATP酶和螺旋酶活性，而且还损害了XPB介导的对3组啮齿动物紫外线敏感突变体修复缺陷的交叉互补作用。XPB的持续功能障碍可能部分是 blast危机中基因组不稳定的基础。
