与BRCA2 C末端的相互作用可保护RAD51-DNA细丝不被BRC重复序列拆解。
Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats.
作者信息
Davies Owen Richard, Pellegrini Luca
机构信息
University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge CB2 1GA, UK.
出版信息
Nat Struct Mol Biol. 2007 Jun;14(6):475-83. doi: 10.1038/nsmb1251.
Abstract
BRCA2 has an essential function in DNA repair by homologous recombination, interacting with RAD51 via short motifs in the middle and at the C terminus of BRCA2. Here, we report that a conserved 36-residue sequence of human BRCA2 encoded by exon 27 (BRCA2Exon27) interacts with RAD51 through the specific recognition of oligomerized RAD51 ATPase domains. BRCA2Exon27 binding stabilizes the RAD51 nucleoprotein filament against disassembly by BRC repeat 4. The protection is specific for RAD51 filaments formed on single-stranded DNA and is lost when BRCA2Exon27 is phosphorylated on Ser3291. We propose that productive recombination results from the functional balance between the different RAD51-binding modes [corrected] of the BRC repeat and exon 27 regions of BRCA2. Our results further suggest a mechanism in which CDK phosphorylation of BRCA2Exon27 at the G2-M transition alters the balance in favor of RAD51 filament disassembly, thus terminating recombination.
摘要
BRCA2在通过同源重组进行的DNA修复中具有重要功能，它通过BRCA2中部和C末端的短基序与RAD51相互作用。在此，我们报告由外显子27编码的人类BRCA2的一个保守的36个残基序列（BRCA2Exon27）通过对寡聚化的RAD51 ATP酶结构域的特异性识别与RAD51相互作用。BRCA2Exon27的结合稳定了RAD51核蛋白丝，使其免受BRC重复序列4的拆解。这种保护作用对在单链DNA上形成的RAD51丝具有特异性，当BRCA2Exon27在Ser3291位点磷酸化时，这种保护作用就会丧失。我们提出，有效的重组源于BRCA2的BRC重复序列和外显子27区域不同RAD51结合模式之间的功能平衡。我们的结果进一步表明了一种机制，即G2-M期转换时BRCA2Exon27的CDK磷酸化改变了平衡，有利于RAD51丝的拆解，从而终止重组。
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