Solution structure of the single-strand break repair protein XRCC1 N-terminal domain

XRCC1 functions in the repair of single-strand DNA breaks in mammalian cell s and forms a repair complex with beta-Pol, ligase III and PARP. Here we de scribe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD ). The structural core is a beta-sandwich with beta-strands connected by lo ops, three helices and two short two-stranded P-sheets at each connection s ide. We show, for the first time, that the XRCC1 NTD specifically binds sin gle-strand break DNA (gapped and nicked). We also show that the XRCC1 NTD b inds a gapped DNA-beta-Pol complex. The DNA binding and beta-Pol binding su rfaces were mapped by NMR and found to be well suited for interaction with single-strand gap DNA containing a 90 degrees bend, and for simultaneously making contacts with the palm-thumb of beta-Pol in a ternary complex. The f indings suggest a mechanism for preferential binding of the XRCC1 NTD to fl exible single-strand break DNA.