BRCC36A is epistatic to BRCA1 in DNA crosslink repair and homologous recombination in Arabidopsis thaliana.

BRCC36A is epistatic to BRCA1 in DNA crosslink repair and homologous recombination in Arabidopsis thaliana.
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DOI:
10.1093/nar/gkq722
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发表时间:
2011-01
影响因子:
14.9
通讯作者:
Puchta H
Puchta H
中科院分区:
生物学2区
文献类型:
--
作者:
Block-Schmidt AS;Dukowic-Schulze S;Wanieck K;Reidt W;Puchta H

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BRCA 1是哺乳动物中一种重要的肿瘤抑制蛋白,参与DNA修复、染色体分离和染色质重塑等多种细胞过程。有趣的是,BRCA 1及其几种复合伴侣的同源物也在植物中发现。由于相应的突变体是可行的,与哺乳动物突变体相反,详细分析其生物学作用是可能的。在这里,我们证明,模式植物拟南芥窝藏两个同源的哺乳动物BRCA 1相互作用伙伴BRCC 36,AtBRCC 36 A和AtBRCC 36 B。两个基因的突变体以及双突变体都是完全可育的,并且在发育中没有缺陷。我们能够表明,突变的同源物之一,AtBRCC 36 A,导致严重的缺陷内和染色体间同源重组(HR)。HR缺陷在Atbrca 1突变体中也很明显。由于Atbrcc 36 a/Atbrca 1双突变体的行为与AtBRCA 1和AtBRCC 36 A单突变体相似,因此这两种蛋白似乎参与了HR调节的共同途径。AtBRCC 36在DNA交联修复中也对AtBRCA 1具有上位性。在遗传毒性应激时,AtBRCC 36 A被转移到细胞核中。
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.
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