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ATP for the DNA ligation step in base excision repair is generated from poly(ADP-ribose)
1Institut für Biochemie, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Federal Republic of Germany. lity@zedat.fu-berlin.de
The Journal of Biological Chemistry
|August 10, 2000
Summary
Poly(ADP-ribose) fuels the final step of base excision repair (BER) in mammalian cells. This process generates ATP from poly(ADP-ribose) to power DNA ligation, crucial for repairing DNA lesions.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- The base excision repair (BER) pathway is vital for counteracting DNA damage in mammalian cells.
- DNA nicks trigger DNA polymerase activity and poly(ADP-ribose) synthesis.
Purpose of the Study:
- To investigate the role of poly(ADP-ribose) in the base excision repair pathway.
- To elucidate the energy source for the DNA ligation step in BER.
Main Methods:
- Experiments using radiolabeled poly(ADP-ribose) and NAD in HeLa nuclear extracts.
- Tracking the metabolic fate of poly(ADP-ribose) and NAD during DNA repair.
- Investigating the effect of 3-aminobenzamide on the BER pathway.
Main Results:
- Poly(ADP-ribose) is converted to ATP, serving as an energy source for DNA ligation.
- ATP synthesis from poly(ADP-ribose) is dependent on nick-induced DNA synthesis.
- The adenylyl moiety from ATP is transferred to DNA ligase III for DNA repair.
Conclusions:
- Poly(ADP-ribose) is essential for the rate-limiting DNA ligation step in BER.
- Poly(ADP-ribose) polymerase-1, DNA polymerase beta, and ligase III form a complex with x-ray repair cross-complementing protein-1.
- This BER complex ensures ATP generation and its specific utilization for DNA ligation.