ATM

Cilia effects upon perturbation of ATM

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.90) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Increased Signaling (Negative Regulator) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Human ciliopathy phenotype:

ataxia telangiectasia; Ataxia-telangiectasia; Ataxia-telangiectasia variant; ataxia - telangiectasia variant

Ciliopathy associations

• Ataxia-Telangiectasia-like Disorder

Subcellular localization

cilia associated gene, nucleoplasm, vesicles

Functional category

• Ciliary assembly/disassembly

Function

Mechanistically, ataxia telangiectasia mutated (ATM) and ATM and RAD3-related (ATR), tumor suppressors that initiate DNA damage responses, promoted the excessive formation of centriolar satellites (EFoCS) and autophagy activation. Disruption of EFoCS and autophagy inhibited primary ciliogenesis, sensitizing PDAC cells to cisplatin treatment. Collectively, our findings revealed an unexpected interplay among the DNA damage response, primary cilia, and chemoresistance in PDAC and deciphered the molecular mechanism by which ATM/ATR-mediated EFoCS and autophagy cooperatively regulate primary ciliogenesis(PMID: 36251015).