WRN interacts physically and functionally with the recombination mediator protein RAD52
WRN interacts physically and functionally with the recombination mediator protein RAD52
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DOI：
10.1074/jbc.m303885200
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发表时间：
2003-09-19
影响因子：
4.8
通讯作者：
Seeberg, E
中科院分区：
文献类型：
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作者：
Baynton, K;Otterlei, M;Seeberg, E
维尔纳综合征 (WS) 是一种过早衰老疾病，使受影响的个体容易患上癌症。受影响的基因 WRN 编码 RecQ 同源物，其精确的生物学功能仍然难以捉摸。 DNA 重组改变是 WS 细胞的标志，表明 WRN 在这些途径中发挥着重要作用。在这里，我们报告了 WRN 和同源重组介导蛋白 RAD52 之间的一种新的物理和功能相互作用。荧光共振能量转移 (FRET) 分析表明，WRN 和 RAD52 在体内形成复合物，共定位于与停滞的复制叉相关的病灶中。生化研究表明，RAD52 以 DNA 结构依赖性方式抑制和增强 WRN 解旋酶活性，而 WRN 则提高 RAD52 介导的非双链 DNA 与双链质粒中包含的同源序列之间链退火的效率。这些结果表明，协调的 WRN 和 RAD52 活性参与 DNA 损伤后的复制叉救援。
Werner syndrome (WS) is a premature aging disorder that predisposes affected individuals to cancer development. The affected gene, WRN, encodes an RecQ homologue whose precise biological function remains elusive. Altered DNA recombination is a hallmark of WS cells suggesting that WRN plays an important role in these pathways. Here we report a novel physical and functional interaction between WRN and the homologous recombination mediator protein RAD52. Fluorescence resonance energy transfer ( FRET) analyses show that WRN and RAD52 form a complex in vivo that co-localizes in foci associated with arrested replication forks. Biochemical studies demonstrate that RAD52 both inhibits and enhances WRN helicase activity in a DNA structure-dependent manner, whereas WRN increases the efficiency of RAD52-mediated strand annealing between non-duplex DNA and homologous sequences contained within a double-stranded plasmid. These results suggest that coordinated WRN and RAD52 activities are involved in replication fork rescue after DNA damage.