ATP-dependent selection between single nucleotide and long patch base excision repair |
| |
Authors: | Petermann Eva Ziegler Mathias Oei Shiao Li |
| |
Institution: | 1. State Research Institute Centre for Innovative Medicine, Santariskiu St. 5, LT-08406 Vilnius, Lithuania;2. Vilnius University, Faculty of Medicine, Center of Rheumatology, Santariskiu St. 2, LT-08661 Vilnius, Lithuania;1. Department of Zoology, University of Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain;2. Department of Cell Biology, University of Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain;3. Department of Ecology, University of Granada, Avda. Fuentenueva s/n, E-18071 Granada, Spain;4. Estación de Fotobiología Playa Unión, PO Box 15., U9103 Rawson, Chubut, Argentina |
| |
Abstract: | DNA base excision repair (BER) constitutes a major mechanism to restore the integrity of the genome following modifications of nucleobases. Although it is well established that poly(ADP-ribosylation) facilitates BER, the mechanism of this stimulation has remained unknown. Previous observations suggested that poly(ADP-ribose), which is synthesised from NAD(+), could serve as a unique source of ATP required for the ligation step in BER. This pathway of ATP generation is thought to compensate ATP shortage and relies on the release of pyrophosphate during DNA repair synthesis. Here, we present evidence that, in situations of cellular energy depletion, the synthesis of poly(ADP-ribose) is indeed stimulated. Simultaneously, single nucleotide repair is reduced. Rather, the number of nucleotides incorporated by DNA polymerase beta (Pol beta) during DNA repair synthesis is increased. Using a reconstituted system including the recombinant BER proteins Pol beta, AP endonuclease 1 (APE 1), X-ray repair cross-complementing group-1 (XRCC1), DNA ligase III (Lig III), flap endonuclease 1 (FEN 1), and poly(ADP-ribose) polymerase-1 (PARP-1), it is demonstrated that in the absence of ATP, both long patch DNA synthesis by Pol beta and poly(ADP-ribosylation) catalysed by PARP-1 are stimulated. Consequently, the preferred use of either long patch or single nucleotide BER depends on the availability of ATP. It is proposed that long patch BER is required for ATP generation from poly(ADP-ribose) and, therefore, predominant under conditions of ATP shortage. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|