Assessing the link between BACH1 and BRCA1 in the FA pathway
Assessing the link between BACH1 and BRCA1 in the FA pathway
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DOI：
10.4161/cc.5.2.2338
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发表时间：
2006-01-16
期刊：
影响因子：
4.3
通讯作者：
Andreassen, PR
中科院分区：
文献类型：
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作者：
Cantor, SB;Andreassen, PR
BACH 1解旋酶最初通过与BRCA 1的直接结合而被鉴定，因此与遗传性乳腺癌有关。最近，BACH 1被鉴定为范可尼贫血（FA）J互补组中的基因缺陷。FA是一种多遗传性疾病，其特征在于细胞对交联剂的敏感性和染色体不稳定性。由于FANCD 2单泛素化在BACH 1缺陷细胞中是完整的，因此BACH 1似乎在FA途径的下游起作用，类似于BRCA 2/FANCD 1。有趣的是，虽然BRCA 1与FA蛋白有各种相互作用，但它尚未被鉴定为FA基因。随着发现最后几个未知FA互补基团的竞赛即将结束，未来的工作将需要揭示这些基因产物如何发挥作用以对抗DNA损伤的影响并保持基因组稳定性。特别是，BRCA 1是否通过与BACH 1/FANCJ的相互作用在功能上与FA途径相关仍然难以捉摸。本文综述了FA通路中BRCA 1与BACH 1的连接模型。我们预测BRCA 1调节BACH 1解旋酶活性，以协调Rad 51从核丝的及时置换，促进无错误修复并最终维持染色体完整性。
The BACH1 helicase was initially identified by its direct binding to BRCA1 and, thus, was linked to hereditary breast cancer. More recently, BACH1 was identified as the gene defective in the J complementation group of Fanconi anemia (FA). FA is a multigenetic disorder characterized by cellular sensitivity to crosslinkers and chromosome instability. Because FANCD2 monoubiquitination is intact in BACH1 deficient cells, BACH1 appears to act downstream in the FA pathway akin to BRCA2/FANCD1. Interestingly, while BRCA1 has various interactions with FA proteins it has not been identified as an FA gene. As the race to uncover the last few unknown FA complementation groups comes to an end, future work will be required to uncover how these gene products function to combat the effects of DNA damage and maintain genomic stability. In particular, it remains elusive whether BRCA1 is functionally linked to the FA pathway through its interaction with BACH1/FANCJ. This review focuses on a model for the connection of BRCA1 to BACH1 in the FA pathway. We predict that BRCA1 regulates the BACH1 helicase activity to coordinate the timely displacement of Rad51 from nucleofilaments, promoting error free repair and ultimately maintaining chromosomal integrity.