Welcome to CDC stacks | Tyrosyl-DNA Phosphodiesterase I a critical survival factor for neuronal development and homeostasis - 42192 | CDC Public Access
Stacks Logo
Advanced Search
Select up to three search categories and corresponding keywords using the fields to the right. Refer to the Help section for more detailed instructions.
Clear All Simple Search
Advanced Search
Tyrosyl-DNA Phosphodiesterase I a critical survival factor for neuronal development and homeostasis
  • Published Date:
  • Source:
    J Neurol Neuromedicine. 1(5):25-29.
Filetype[PDF-476.71 KB]

  • Keywords:
  • Pubmed ID:
  • Pubmed Central ID:
  • Description:
    Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H(493)R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex. The ATM kinase activates proteins early on in response to DNA damage. Tdp1-/- and Atm-/- mice exhibit accumulation of DNA topoisomerase I-DNA covalent complexes (TOPO1-cc) explicitly in neuronal tissue during development. TDP1 resolves 3'- and 5'-DNA adducts including trapped TOPO1-cc and TOPO1 protease resistant peptide-DNA complex. ATM appears to regulate the response to TOPO1-cc via a noncanonical function by regulating SUMO/ubiquitin-mediated TOPO1 degradation. In conclusion, TDP1 and ATM are critical factors for neuronal cell viability via two independent but cooperative pathways.

  • Document Type:
  • Collection(s):
  • Funding:
    K08 CA131483/BC/NCI NIH HHS/United States
    P30 CA013148/CA/NCI NIH HHS/United States
    R00 CA131489/CA/NCI NIH HHS/United States
    R00 CA131489/BC/NCI NIH HHS/United States
    P30 CA013148/BC/NCI NIH HHS/United States
    K08 CA131483/CA/NCI NIH HHS/United States
    U58 SO000004/SO/PHSPO CDC HHS/United States
No Related Documents.
You May Also Like: