Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.
Mol Cell. 2010 Sep 24;39(6):862-72. doi: 10.1016/j.molcel.2010.08.028.
Purified DNA translocases Rdh54 and Rad54 can dissociate complexes formed by eukaryotic RecA-like recombinases on double-stranded DNA. Here, we show that Rad51 complexes are dissociated by these translocases in mitotic cells. Rad51 overexpression blocked growth of cells deficient in Rdh54 activity. This toxicity was associated with accumulation of Rad51 foci on undamaged chromatin. At normal Rad51 levels, rdh54 deficiency resulted in slight elevation of Rad51 foci. A triple mutant lacking Rdh54, Rad54, and a third Swi2/Snf2 homolog Uls1 accumulated Rad51 foci, grew slowly, and suffered chromosome loss. Thus, Uls1 and Rad54 can partially substitute for Rdh54 in the removal of toxic, nondamage-associated Rad51-DNA complexes. Additional data suggest that the function of Rdh54 and Rad54 in removal of Rad51 foci is significantly specialized; Rad54 predominates for removal of damage-associated foci, and Rdh54 predominates for removal of nondamage-associated foci.
纯化的 DNA 转位酶 Rdh54 和 Rad54 可以解离真核 RecA 样重组酶在双链 DNA 上形成的复合物。在这里，我们表明这些转位酶可以在有丝分裂细胞中解离 Rad51 复合物。Rad51 的过表达阻止了 Rdh54 活性缺失细胞的生长。这种毒性与未受损染色质上 Rad51 焦点的积累有关。在正常 Rad51 水平下，rdh54 缺失导致 Rad51 焦点轻微升高。缺乏 Rdh54、Rad54 和第三个 Swi2/Snf2 同源物 Uls1 的三突变体积累 Rad51 焦点，生长缓慢，并遭受染色体丢失。因此，Uls1 和 Rad54 可以部分替代 Rdh54 来去除有毒的、非损伤相关的 Rad51-DNA 复合物。更多的数据表明，Rdh54 和 Rad54 在去除 Rad51 焦点方面的功能具有显著的特异性；Rad54 主要用于去除损伤相关的焦点，而 Rdh54 主要用于去除非损伤相关的焦点。
