ATPase family AAA domain-containing protein 5 (ATAD5)

ATPase family AAA domain-containing protein 5 (ATAD5) is an AAA+ ATPase and a key component of a Replication Factor C (RFC)-like complex responsible for unloading the DNA polymerase processivity factor, PCNA, from chromatin following completion of DNA replication. It ensures proper progression and completion of DNA replication, maintains genome stability, and coordinates responses to DNA damage, facilitating repair or apoptosis when necessary. ATAD5 docks with PCNA and other replisome proteins through its conserved ATPase domain and modulates PCNA ubiquitylation by recruiting the deubiquitination machinery. Deficiency of ATAD5 leads to defective PCNA unloading, increased chromatin retention of replication proteins, S-phase progression delays, persistent DNA damage signaling, and heightened sensitivity to DNA-damaging agents. Mutations or reduced expression of ATAD5 are implicated in cancer predisposition through induction of chromosome fragility and genomic instability[1][4][6][5].

Other names

C17orf41ELG1FRAG1chromosome fragility-associated gene 1 proteinenhanced level of genomic instability 1 homologFLJ12735chromosome fragility associated gene 1

Not applicable (no known drugs specifically target ATAD5 directly); experimentally, ATAD5 loss sensitizes cells to DNA damaging agents due to impaired DNA repair/unloading of PCNA[2].