Magner Daniel B, Blankschien Matthew D, Lee Jennifer A, Pennington Jeanine M, Lupski James R, Rosenberg Susan M
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Mol Cell. 2007 Apr 27;26(2):273-86. doi: 10.1016/j.molcel.2007.03.012.
The RecQ-helicase family is widespread, is highly conserved, and includes human orthologs that suppress genomic instability and cancer. In vivo, some RecQ homologs promote reduction of steady-state levels of bimolecular recombination intermediates (BRIs), which block chromosome segregation if not resolved. We find that, in vivo, E. coli RecQ can promote the opposite: the net accumulation of BRIs. We report that cells lacking Ruv and UvrD BRI-resolution and -prevention proteins die and display failed chromosome segregation attributable to accumulation of BRIs. Death and segregation failure require RecA and RecF strand exchange proteins. FISH data show that replication is completed during chromosome-segregation failure/death of ruv uvrD recA(Ts) cells. Surprisingly, RecQ (and RecJ) promotes this death. The data imply that RecQ promotes the net accumulation of BRIs in vivo, indicating a second paradigm for the in vivo effect of RecQ-like proteins. The E. coli RecQ paradigm may provide a useful model for some human RecQ homologs.
RecQ解旋酶家族分布广泛、高度保守，其中包括抑制基因组不稳定和癌症的人类直系同源基因。在体内，一些RecQ同源物可促进双分子重组中间体（BRI）稳态水平的降低，若不解决这些中间体，会阻碍染色体分离。我们发现，在体内，大肠杆菌RecQ可产生相反的作用：促进BRI的净积累。我们报告称，缺乏Ruv和UvrD BRI解决和预防蛋白的细胞会死亡，并因BRI积累而出现染色体分离失败。细胞死亡和分离失败需要RecA和RecF链交换蛋白。荧光原位杂交（FISH）数据显示，在ruv uvrD recA（Ts）细胞的染色体分离失败/死亡过程中复制完成。令人惊讶的是，RecQ（和RecJ）会促使细胞死亡。这些数据表明，RecQ在体内促进了BRI的净积累，这表明了RecQ样蛋白体内作用的第二种模式。大肠杆菌RecQ模式可能为一些人类RecQ同源物提供有用的模型。
