ATAD5
Description
The ATAD5 (ATPase family AAA domain containing 5) is a protein-coding gene located on chromosome 17.
ATAD5, also known as Chromosome fragility-associated gene 1 protein, is a crucial component of DNA replication and genome integrity maintenance during replication stress. It plays a role in the RAD9A-related damage checkpoint, influencing cell fate in response to DNA damage. ATAD5 interacts with various proteins, including RAD9A, BCL2, USP1, WDR48, PCNA, RAD51, and BRD4. It forms part of the ATAD5 RFC-like complex, which regulates PCNA function during DNA replication. ATAD5's interactions and activities are critical for managing DNA replication, preventing errors, and restarting stalled replication forks.
ATAD5 plays a crucial role in DNA replication and maintaining genome integrity during replication stress. It participates in the RAD9A-related damage checkpoint, which determines whether DNA damage triggers cell survival or apoptosis. ATAD5 modulates the interaction between RAD9A and BCL2, inducing apoptosis in response to DNA damage. Furthermore, it promotes PCNA deubiquitination by recruiting USP1 and WDR48, downregulating the error-prone damage bypass pathway. As a component of the ATAD5 RFC-like complex, ATAD5 regulates PCNA function by unloading the PCNA homotrimer from DNA after replication during the S phase, a process dependent on its ATPase activity. ATAD5 also plays a significant role in restarting stalled replication forks under replication stress by unloading PCNA and recruiting RAD51, potentially through an ATR-dependent mechanism. This leads to replication fork regression, breakage, and eventual restart. Both PCNA unloading activity and interaction with WDR48 are necessary for efficient RAD51 recruitment to stalled replication forks. ATAD5 promotes MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, offering an alternative pathway for restarting stalled or regressed replication forks. {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}
ATAD5 is also known as C17orf41, ELG1, FRAG1.
