APLF
Domain
The PBZ-type zinc fingers (also named CYR) mediate non-covalent poly-ADP-ribose-binding (PubMed:18172500, PubMed:18474613, PubMed:30104678). Specifically recognizes branched poly-ADP-ribose chains generated by PARP2 (PubMed:30104678). Poly-ADP-ribose-binding is dependent on the presence of zinc and promotes its recruitment to DNA damage sites (PubMed:18172500, PubMed:18474613).
The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites.
The FHA-like domain mediates interaction with XRCC1 and XRCC4.
The NAP1L motif is required for the histone chaperone activity.
Function
Histone chaperone involved in single-strand and double-strand DNA break repair (PubMed:17353262, PubMed:17396150, PubMed:21211721, PubMed:21211722, PubMed:29905837, PubMed:30104678). Recruited to sites of DNA damage through interaction with branched poly-ADP-ribose chains, a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions (PubMed:17353262, PubMed:17396150, PubMed:21211721, PubMed:30104678). Following recruitment to DNA damage sites, acts as a histone chaperone that mediates histone eviction during DNA repair and promotes recruitment of histone variant MACROH2A1 (PubMed:21211722, PubMed:29905837, PubMed:30104678). Also has a nuclease activity: displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro (PubMed:17353262, PubMed:17396150). Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage (PubMed:17353262, PubMed:17396150). Together with PARP3, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721, PubMed:23689425). Also acts as a negative regulator of cell pluripotency by promoting histone exchange (By similarity). Required for the embryo implantation during the epithelial to mesenchymal transition in females (By similarity).
Post-translational modifications
Poly-ADP-ribosylated. In addition to binding non covalently poly-ADP-ribose via its PBZ-type zinc fingers, the protein is also covalently poly-ADP-ribosylated by PARP1.
Phosphorylated in an ATM-dependent manner upon double-strand DNA break.
Sequence Similarities
Belongs to the APLF family.
Cellular localization
- Nucleus
- Chromosome
- Cytoplasm
- Cytosol
- Localizes to DNA damage sites (PubMed:18172500, PubMed:18474613, PubMed:21211721, PubMed:21211722, PubMed:23689425). Accumulates at single-strand breaks and double-strand breaks via the PBZ-type zinc fingers (PubMed:18172500).
Alternative names
C2orf13, PALF, XIP1, APLF, Aprataxin and PNK-like factor, Apurinic-apyrimidinic endonuclease APLF, PNK and APTX-like FHA domain-containing protein, XRCC1-interacting protein 1