XRCC1 functions in the repair of single-strand DNA breaks in mammalian cells and forms a repair complex with beta-Pol, ligase III and PARP. Here we describe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD). The structural core is a beta-sandwich with beta-strands connected by loops, three helices and two short two-stranded beta-sheets at each connection side. We show, for the first time, that the XRCC1 NTD specifically binds single-strand break DNA (gapped and nicked). We also show that the XRCC1 NTD binds a gapped DNA-beta-Pol complex. The DNA binding and beta-Pol binding surfaces 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 findings suggest a mechanism for preferential binding of the XRCC1 NTD to flexible single-strand break DNA.
Solution structure of the single-strand break repair protein XRCC1 N-terminal domain.,Marintchev A, Mullen MA, Maciejewski MW, Pan B, Gryk MR, Mullen GP Nat Struct Biol. 1999 Sep;6(9):884-93. PMID:10467102
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑ Marintchev A, Mullen MA, Maciejewski MW, Pan B, Gryk MR, Mullen GP. Solution structure of the single-strand break repair protein XRCC1 N-terminal domain. Nat Struct Biol. 1999 Sep;6(9):884-93. PMID:10467102 doi:10.1038/12347