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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/29632

Title: Characterization of APLF in Non-homologous End-joining
Authors: Shirodkar, Purnata V.
Advisor: Koch, Christine Anne
Department: Medical Biophysics
Keywords: APLF
Non-homologous End-joining
Ku
nuclear localization
Issue Date: 25-Aug-2011
Abstract: APLF (Aprataxin and Polynucleotide kinase-Like Factor), a novel protein with a forkhead-associated (FHA) domain and two poly(ADP-ribose)-binding zinc fingers (PBZ), interacts with core non-homologous end-joining (NHEJ) repair factors, Ku and XRCC4-DNA ligase IV, and facilitates NHEJ. However, how APLF functions in NHEJ is undefined. This thesis demonstrates that the Ku-binding domain on APLF is mapped to amino acid residues 180-200, where conserved amino acid residue W189 strongly contributes to the APLF-Ku interaction. Remarkably, the APLF-Ku interaction is involved in the nuclear localization of APLF. Furthermore, we demonstrate that the N-terminal region (amino acids 1-200), containing the XRCC4-Ligase IV and Ku binding domains, is required for APLF- dependent NHEJ. Collectively, these findings suggest that Ku contributes to APLF nuclear localization, and that once APLF is retained in the nucleus, the N-terminal portion of APLF, which facilitates interactions with the core NHEJ proteins Ku and XRCC4-DNA ligase IV, is required for efficient NHEJ.
URI: http://hdl.handle.net/1807/29632
Appears in Collections:Master

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