| Autor: |
Pachkowski BF; Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA., Tano K, Afonin V, Elder RH, Takeda S, Watanabe M, Swenberg JA, Nakamura J |
| Jazyk: |
angličtina |
| Zdroj: |
Mutation research [Mutat Res] 2009 Dec 01; Vol. 671 (1-2), pp. 93-9. Date of Electronic Publication: 2009 Sep 22. |
| DOI: |
10.1016/j.mrfmmm.2009.09.006 |
| Abstrakt: |
Poly(ADP-ribose) polymerase-1 (PARP-1) is a base excision repair (BER) protein that binds to DNA single strand breaks (SSBs) and subsequently synthesizes and transfers poly(ADP-ribose) polymers to various nuclear proteins. Numerous biochemical studies have implicated PARP-1 as a modulator of BER; however, the role of PARP-1 in BER in living cells remains unclear partly due to lack of accurate quantitation of BER intermediates existing in cells. Since DT40 cells, chicken B lymphocytes, naturally lack PARP-2, DT40 cells allow for the investigation of the PARP-1 null phenotype without confounding by PARP-2. To test the hypothesis that PARP-1 is necessary for efficient BER during methylmethane sulfonate (MMS) exposure in vertebrate cells, intact DT40 cells and their isogenic PARP-1 null counterparts were challenged with different exposure scenarios for phenotypic characterization. With chronic exposure, PARP-1 null cells exhibited sensitivity to MMS but with an acute exposure did not accumulate base lesions or AP sites to a greater extent than wild-type cells. However, an increase in SSB content in PARP-1 null cell DNA, as indicated by glyoxal gel electrophoresis under neutral conditions, suggested the presence of BER intermediates. These data suggest that during exposure, PARP-1 impacts the stage of BER after excision of the deoxyribosephosphate moiety from the 5' end of DNA strand breaks by polymerase beta. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect