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Related Experiment Videos

ATP-dependent selection between single nucleotide and long patch base excision repair.

Eva Petermann1, Mathias Ziegler, Shiao Li Oei

  • 1Institut für Biochemie, Freie Universität Berlin, Thielallee 63, 14195, Berlin, Germany.

DNA Repair
|September 19, 2003
PubMed
Summary
This summary is machine-generated.

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Poly(ADP-ribosylation) stimulates DNA repair synthesis when cellular ATP is low. This process favors long-patch base excision repair (BER) for ATP generation, enhancing genome integrity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA base excision repair (BER) is crucial for maintaining genome integrity against nucleobase damage.
  • Poly(ADP-ribosylation) is known to facilitate BER, but the underlying mechanism remains unclear.
  • Poly(ADP-ribose) synthesis from NAD(+) may provide ATP for BER ligation, especially during energy depletion.

Purpose of the Study:

  • To elucidate the mechanism by which poly(ADP-ribosylation) stimulates DNA base excision repair (BER).
  • To investigate the role of poly(ADP-ribose) as an ATP source during DNA repair synthesis.
  • To determine the conditions under which single nucleotide versus long patch BER is preferred.

Main Methods:

  • Studied DNA repair synthesis in cellular energy depletion models.

Related Experiment Videos

  • Utilized a reconstituted in vitro system with recombinant BER proteins: Pol beta, APE 1, XRCC1, Lig III, FEN 1, and PARP-1.
  • Assessed DNA synthesis and poly(ADP-ribosylation) in the presence and absence of ATP.

    • Main Results:

    • Cellular energy depletion stimulated poly(ADP-ribosylation) synthesis and increased nucleotide incorporation during DNA repair synthesis.
    • Single nucleotide BER was reduced, while long patch DNA synthesis by DNA polymerase beta (Pol beta) was enhanced under ATP-limiting conditions.
    • In a reconstituted system, both long patch DNA synthesis by Pol beta and poly(ADP-ribosylation) by PARP-1 were stimulated in the absence of ATP.

    Conclusions:

    • The choice between long patch and single nucleotide BER is dependent on cellular ATP availability.
    • Long patch BER is proposed to be essential for generating ATP from poly(ADP-ribose) during periods of ATP shortage.
    • This mechanism highlights a novel role for poly(ADP-ribosylation) in energy homeostasis and genome maintenance.