Open AccessPolyADP‐ribosylation and cancer
Author(s) -
Miwa Masanao,
Masutani Mitsuko
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00567.x
Subject(s) - carcinogenesis , poly adp ribose polymerase , dna repair , cancer , biology , genome instability , cancer research , dna damage , parp inhibitor , parp1 , knockout mouse , genetics , polymerase , dna , gene
The polyADP‐ribosylation reaction results in a unique post‐translational modification involved in various cellular processes and conditions, including DNA repair, transcriptional control, genomic stability, cell death and transformation. The existence of 17 members of the poly(ADP‐ribose) polymerase (PARP) family has so far been documented, with overlapping functional consequences. PARP‐1 is known to be involved in DNA base excision repair and this explains the susceptibility spectrum of PARP‐1 knockout animals to genotoxic carcinogens. The fact that centrosome amplification is induced by a non‐genotoxic inhibitor of PARP and in PARP‐1 knockout mouse cells, is in line with aneuploidy, which is frequent in cancers. Genetically engineered animal models have revealed that PARP‐1 and VPARP impact carcinogenesis. Furthermore, accumulating experimental evidence supports the utility of PARP and PARG inhibitors in cancer therapy and several clinical trials are now ongoing. Increasing NAD + levels by pharmacological supplementation with niacin has also been found to exert preventive effects against cancer. In the present review, recent research progress on polyADP‐ribosylation related to neoplasia is summarized and discussed. ( Cancer Sci 2007; 98: 1528–1535)