2r9a: Difference between revisions

DNA double-strand breaks represent one of the most severe forms of DNA damage in mammalian cells. One pathway for repairing these breaks occurs via nonhomologous end-joining (NHEJ) and depends on XRCC4, LigaseIV, and Cernunnos, also called XLF. Although XLF stimulates XRCC4/LigaseIV to ligate mismatched and noncohesive DNA ends, the mechanistic basis for this function remains unclear. Here we report the structure of a partially functional 224 residue N-terminal fragment of human XLF. Despite only weak sequence similarity, XLF(1-170) shares structural homology with XRCC4(1-159). However, unlike the highly extended 130 A helical domain observed in XRCC4, XLF adopts a more compact, folded helical C-terminal region involving two turns and a twist, wrapping back to the structurally conserved N terminus. Mutational analysis of XLF and XRCC4 reveals a potential interaction interface, suggesting a mechanism for how XLF stimulates the ligation of mismatched ends.

Crystal structure of human XLF: a twist in nonhomologous DNA end-joining., Andres SN, Modesti M, Tsai CJ, Chu G, Junop MS, Mol Cell. 2007 Dec 28;28(6):1093-101. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18158905 18158905]

[[Category: Andres, S N.]]

[[Category: Junop, M S.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:45:37 2008''