Danilowicz Claudia, Hermans Laura, Coljee Vincent, Prévost Chantal, Prentiss Mara
Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Laboratoire de Biochimie Théorique, CNRS UMR 9080, IBPC, Paris, France.
Nucleic Acids Res. 2017 Aug 21;45(14):8448-8462. doi: 10.1093/nar/gkx582.
During DNA recombination and repair, RecA family proteins must promote rapid joining of homologous DNA. Repeated sequences with >100 base pair lengths occupy more than 1% of bacterial genomes; however, commitment to strand exchange was believed to occur after testing ∼20-30 bp. If that were true, pairings between different copies of long repeated sequences would usually become irreversible. Our experiments reveal that in the presence of ATP hydrolysis even 75 bp sequence-matched strand exchange products remain quite reversible. Experiments also indicate that when ATP hydrolysis is present, flanking heterologous dsDNA regions increase the reversibility of sequence matched strand exchange products with lengths up to ∼75 bp. Results of molecular dynamics simulations provide insight into how ATP hydrolysis destabilizes strand exchange products. These results inspired a model that shows how pairings between long repeated sequences could be efficiently rejected even though most homologous pairings form irreversible products.
在DNA重组和修复过程中，RecA家族蛋白必须促进同源DNA的快速连接。长度超过100个碱基对的重复序列占细菌基因组的1%以上；然而，人们认为在检测约20 - 30个碱基对后才会进行链交换。如果真是这样，长重复序列不同拷贝之间的配对通常会变得不可逆。我们的实验表明，在ATP水解存在的情况下，即使是75个碱基对的序列匹配链交换产物仍然相当可逆。实验还表明，当存在ATP水解时，侧翼异源双链DNA区域会增加长度达约75个碱基对的序列匹配链交换产物的可逆性。分子动力学模拟结果有助于深入了解ATP水解如何使链交换产物不稳定。这些结果启发了一个模型，该模型展示了即使大多数同源配对形成不可逆产物，长重复序列之间的配对如何能够被有效排除。
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