Department of Physical Sciences, Rhode Island College, 600 Mt. Pleasant Ave, Providence, RI 02908-1991, USA.
Protein J. 2011 Jan;30(1):1-8. doi: 10.1007/s10930-010-9295-8.
The American Cancer Society's 2009 statistics estimate that 1 out of every 4 deaths is cancer related. Genomic instability is a common feature of cancerous states, and an increase in genomic instability is the diagnostic feature of Bloom Syndrome. Bloom Syndrome, a rare disorder characterized by a predisposition to cancer, is caused by mutations of the BLM gene. This study focuses on the partnerships of BLM protein to RAD51, a Homologous Recombination repair protein essential for survival. A systematic set of BLM deletion fragments were generated to refine the protein binding domains of BLM to RAD51 and determine interacting regions of BLM and ssDNA. Results show that RAD51 and ssDNA interact in overlapping regions; BLM₁₀₀₋₂₁₄ and BLM₁₃₁₇₋₁₃₆₇. The overlapping nature of these regions suggests a preferential binding for one partner that could function to regulate homologous recombination and therefore helps to clarify the role of BLM in maintaining genomic stability.
美国癌症协会 2009 年的统计数据估计,每 4 例死亡中就有 1 例与癌症有关。基因组不稳定性是癌症状态的一个常见特征,而基因组不稳定性的增加是布卢姆综合征的诊断特征。布卢姆综合征是一种罕见的疾病,其特征是易患癌症,由 BLM 基因突变引起。本研究专注于 BLM 蛋白与 RAD51 的相互作用,RAD51 是同源重组修复蛋白,对生存至关重要。本研究生成了一系列 BLM 缺失片段,以精确定位 BLM 与 RAD51 的结合域,并确定 BLM 和单链 DNA 的相互作用区域。结果表明,RAD51 和单链 DNA 在重叠区域相互作用;BLM₁₀₋₂₁₄ 和 BLM₁₃₁₇₋₁₃₆₇。这些区域的重叠性质表明,一个伴侣具有优先结合的可能性,这可能有助于调节同源重组,从而有助于阐明 BLM 在维持基因组稳定性中的作用。