Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Although poly(ADP-ribose) polymerase-1 (PARP-1) has no enzymatic activity involved in DNA damage processing by the base excision repair (BER) pathway, PARP-1 deficient cells are genetically unstable and sensitive to DNA-damaging agents. To explain this paradox, we investigated the impact of PARP-1 on BER in mammalian cells. We reduced cellular PARP-1 protein levels using siRNA, then introduced DNA damage by hydrogen peroxide treatment and examined the repair response. We find that PARP-1 is not involved in recruitment of the major BER proteins to sites of DNA damage. However, we find that PARP-1 protects excessive DNA single strand breaks (SSBs) from converting into DNA double strand breaks (DSBs) thus preserving them for subsequent repair by BER enzymes. This suggests that PARP-1 plays an important role in BER by extending the ability of BER enzymes to process DNA single strand breaks arising directly after mutagen stress or during processing of DNA lesions following extensive DNA damage.

Original publication

DOI

10.1016/j.dnarep.2008.03.017

Type

Journal article

Journal

DNA Repair (Amst)

Publication Date

01/06/2008

Volume

7

Pages

932 - 940

Keywords

Base Sequence, Cell Line, Comet Assay, DNA, DNA Damage, DNA Repair, Humans, Hydrogen Peroxide, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases, RNA Interference, RNA, Small Interfering