Karlsruhe Institute of Technology, Botanical Institute II, Karlsruhe, Germany.
Nucleic Acids Res. 2011 Jan;39(1):146-54. doi: 10.1093/nar/gkq722. Epub 2010 Sep 3.
BRCA1 is a well-known tumor suppressor protein in mammals, involved in multiple cellular processes such as DNA repair, chromosome segregation and chromatin remodeling. Interestingly, homologs of BRCA1 and several of its complex partners are also found in plants. As the respective mutants are viable, in contrast to mammalian mutants, detailed analyses of their biological role is possible. Here we demonstrate that the model plant Arabidopsis thaliana harbors two homologs of the mammalian BRCA1 interaction partner BRCC36, AtBRCC36A and AtBRCC36B. Mutants of both genes as well as the double mutants are fully fertile and show no defects in development. We were able to show that mutation of one of the homologs, AtBRCC36A, leads to a severe defect in intra- and interchromosomal homologous recombination (HR). A HR defect is also apparent in Atbrca1 mutants. As the Atbrcc36a/Atbrca1 double mutant behaves like the single mutants of AtBRCA1 and AtBRCC36A both proteins seem to be involved in a common pathway in the regulation of HR. AtBRCC36 is also epistatic to AtBRCA1 in DNA crosslink repair. Upon genotoxic stress, AtBRCC36A is transferred into the nucleus.
BRCA1 是哺乳动物中一种著名的肿瘤抑制蛋白,参与多种细胞过程,如 DNA 修复、染色体分离和染色质重塑。有趣的是,BRCA1 的同源物及其几个复合物伙伴在植物中也有发现。由于相应的突变体是存活的,与哺乳动物的突变体不同,对其生物学功能的详细分析是可能的。在这里,我们证明了模式植物拟南芥含有哺乳动物 BRCA1 相互作用伙伴 BRCC36 的两个同源物,AtBRCC36A 和 AtBRCC36B。这两个基因的突变体以及双突变体都是完全可育的,在发育过程中没有缺陷。我们能够证明,一个同源物 AtBRCC36A 的突变会导致染色体内和染色体间同源重组(HR)的严重缺陷。Atbrca1 突变体也表现出 HR 缺陷。由于 Atbrcc36a/Atbrca1 双突变体的行为与 AtBRCA1 和 AtBRCC36A 的单突变体相似,这两种蛋白似乎都参与了 HR 调控的共同途径。AtBRCC36 在 DNA 交联修复中也与 AtBRCA1 上位。在遗传毒性应激下,AtBRCC36A 被转移到细胞核内。