Abstract
The RecA family of proteins is essential in homologous recombination, a critical step in DNA repair. Here, we report that a rationally-designed small peptide based on the crystal structure of Escherichia coli RecA-DNA complex can promote homologous recombination through the enhancement of both RecA-mediated strand assimilation and three-strand exchange activity. Among 17 peptides tested, peptide #3 with the amino acid sequence of IRFLTARRR has the most potent activity in promoting the RecA-mediated D-loop formation by approximately 7.2-fold at 37 degrees C. Other peptides such as IRFLTAKKK and IRLLTARRR also have similar, albeit lower, activities. Therefore, hydrophobicity and poly-positive charges, and the space between them in those small peptides are crucial features for such activities. The enhancement of recombination by these peptides appears to be a general phenomenon as similar results were seen by using different plasmids. Remarkably, peptide #3 alone without RecA can also promote the D-loop formation at elevated temperature. Cell viability assays showed that the peptide elevates mammalian cell resistance to two cytotoxic DNA drugs, cisplatin and doxorubicin. The rescue of viability may result from increased DNA repair efficiency. Such peptides may find future biological applications.