Non-homologous end-joining partners in a helical dance: structural studies of XLF–XRCC4 interactions. (21st September 2011)

• Record Type: Journal Article
• Authors: Wu, Qian; Ochi, Takashi; Matak-Vinkovic, Dijana; Robinson, Carol V.; Chirgadze, Dimitri Y.; Blundell, Tom L.
• Is Part Of: Biochemical Society transactions. Volume 39:Number 5(2011)
• Page Start: 1387
• Page End: 1392
• Publication Date: 2011-09-21
• Subjects: double-strand break (DSB) -- non-homologous end-joining (NHEJ) -- X-ray cross-complementation group 4 (XRCC4) -- XRCC4-like factor (XLF); Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0391387
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : XRCC4 (X-ray cross-complementation group 4) and XLF (XRCC4-like factor) are two essential interacting proteins in the human NHEJ (non-homologous end-joining) pathway that repairs DNA DSBs (double-strand breaks). The individual crystal structures show that the dimeric proteins are homologues with protomers containing head domains and helical coiled-coil tails related by approximate two-fold symmetry. Biochemical, mutagenesis, biophysical and structural studies have identified the regions of interaction between the two proteins and suggested models for the XLF–XRCC4 complex. An 8.5 Å (1 Å=0.1 nm) resolution crystal structure of XLF–XRCC4 solved by molecular replacement, together with gel filtration and nano-ESI (nano-electrospray ionization)–MS results, demonstrates that XLF and XRCC4 dimers interact through their head domains and form an alternating left-handed helical structure with polypeptide coiled coils and pseudo-dyads of individual XLF and XRCC4 dimers at right angles to the helical axis.