Aprataxin and polynucleotide kinase–like factor (APLF)

Aprataxin and polynucleotide kinase–like factor (APLF), abbreviated as APLF, is a multifunctional nuclear protein critically involved in DNA repair and chromatin structure regulation[1][2][3]. APLF contains a forkhead-associated (FHA) domain, two PBZ (poly[ADP-ribose] binding zinc finger) motifs, and functions as a scaffold protein that binds phosphorylated DNA repair factors such as XRCC1 and XRCC4, supporting both single- and double-stranded DNA break repair pathways[1][2]. Biochemically, APLF possesses 3′ exonuclease and single-stranded DNA endonuclease activities, enabling it to facilitate DNA end joining during nonhomologous end joining (NHEJ)[2]. Reduction of APLF impairs cellular DNA end joining capacities and cell survival following DNA damage[2]. Uniquely, APLF also acts as a histone chaperone, directly assembling histone octamers (H3-H4 and H2A-H2B) onto DNA to form nucleosomes, an activity distinct from other chaperone proteins[3]. Through these dual activities, APLF supports genome stability and participates in the cellular response to DNA damage. Although not a current pharmacological target, its critical roles make it of interest in the context of genomic stability, cancer, and radiation responses[1][2][3].

Other names

C2orf13PALFMGC47799Xip1ZCCHH1XRCC1-interacting protein 1zinc finger CX5CX6HX5H motif-containing protein 1apurinic-apyrimidinic endonuclease APLFPNK and APTX-like FHA domain–containing protein

Not applicable; no targeted drugs identified as of 2024.