5e50
APLF/XRCC4 complex
Structural highlights
FunctionAPLF_HUMAN Nuclease involved in single-strand and double-strand DNA break repair. Recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro. Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage.[1] [2] Publication Abstract from PubMedAprataxin, aprataxin and PNKP-like factor (APLF) and polynucleotide kinase phosphatase (PNKP) are key DNA-repair proteins with diverse functions but which all contain a homologous forkhead-associated (FHA) domain. Their primary binding targets are casein kinase 2-phosphorylated forms of the XRCC1 and XRCC4 scaffold molecules which respectively coordinate single-stranded and double-stranded DNA break repair pathways. Here, we present the high-resolution X-ray structure of a complex of phosphorylated XRCC4 with APLF, the most divergent of the three FHA domain family members. This, combined with NMR and biochemical analysis of aprataxin and APLF binding to singly and multiply-phosphorylated forms of XRCC1 and XRCC4, and comparison with PNKP reveals a pattern of distinct but overlapping binding specificities that are differentially modulated by multi-site phosphorylation. Together, our data illuminate important differences between activities of the three phospho-binding domains, in spite of a close evolutionary relationship between them. Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by aprataxin-family FHA domains.,Cherry AL, Nott TJ, Kelly G, Rulten SL, Caldecott KW, Smerdon SJ DNA Repair (Amst). 2015 Nov;35:116-25. doi: 10.1016/j.dnarep.2015.10.002. Epub, 2015 Oct 23. PMID:26519825[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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