7月10日，Cancer Cell杂志报道，范可尼贫血肿瘤抑制因子可与乳腺癌抑癌基因BRCA1等联合发挥DNA复制叉保护功能。
范可尼贫血（FA）患者中的突变基因与DNA修复基因BRCA1和BRCA2/FANCD1相互作用抑制肿瘤的发生，但目前归因于它们的分子功能不能完全解释其所有的生物学行为。
本研究显示FA基因（包括FANCD2）和BRCA1基因具有某些与DNA修复无关的功能，例如保护停滞的复制叉免遭降解。令人惊讶的是，在FANCD2缺陷细胞中，升高RAD51水平或稳定RAD51纤维可恢复对复制叉的保护。
此外，FANCD2介导的复制叉保护与RAD51功能存在上位效应，这揭示了一个意料之外的，连接FA基因与RAD51和BRCA1/ 2乳腺癌抑制因子的复制叉保护信号通路。
总之，研究结果提示，FA基因，RAD51和BRCA1/2蛋白共同构成一个分子网络，以不依赖于DNA修复的方式，发挥着防止基因组不稳定性和抑制肿瘤发生的功能。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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A Distinct Replication Fork Protection Pathway Connects Fanconi Anemia Tumor Suppressors to RAD51-BRCA1/2
Katharina Schlacher, Hong Wu, Maria Jasin
Genes mutated in patients with Fanconi anemia (FA) interact with the DNA repair genes BRCA1 and BRCA2/FANCD1 to suppress tumorigenesis, but the molecular functions ascribed to them cannot fully explain all of their cellular roles. Here, we show a repair-independent requirement for FA genes, including FANCD2, and BRCA1 in protecting stalled replication forks from degradation. Fork protection is surprisingly rescued in FANCD2-deficient cells by elevated RAD51 levels or stabilized RAD51 filaments. Moreover, FANCD2-mediated fork protection is epistatic with RAD51 functions, revealing an unanticipated fork protection pathway that connects FA genes to RAD51 and the BRCA1/2 breast cancer suppressors. Collective results imply a unified molecular mechanism for repair-independent functions of FA, RAD51, and BRCA1/2 proteins in preventing genomic instability and suppressing tumorigenesis.
