Am J Cancer Res 2011;1(3):328-346
Review Article
PARP-1 and PARP-2: New players in tumour development
José Yélamos, Jordi Farrés, Laura Llacuna, Coral Ampurdanés, Juan Martin-Caballero
Department of Immunology, Cancer Research Program, IMIM-Hospital del Mar, Barcelona Biomedical Research Park (PRBB),
Barcelona, Spain.
Received December 30, 2010; accepted January 5, 2011; Epub December 6, 2011; Published January 31, 2011
Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 belong to a family of enzymes that, using NAD+ as a substrate,
catalyze poly(ADP-ribosyl)ation of proteins. PARP-1 and PARP-2 catalytic activity is stimulated by DNA-strand breaks targeting
mainly proteins involved in chromatin structure and DNA metabolism, providing strong support for a dual role of both PARP-1
and PARP-2 in the DNA damage response as DNA damage sensors and signal transducers to downstream effectors. The DNA
damage response has important consequences for genomic stability and tumour development. In order to manipulate DNA
damage responses to selectively induce tumour cell death, a considerable effort is centred on defining the molecular
mechanisms that allow cells to detect, respond to, and repair DNA damage. PARP inhibitors that compete with NAD+ at the
highly conserved enzyme active site are arisen as new potential therapeutic strategies as chemo- and radiopotentiation and for
the treatment of cancers with specific DNA repair defects as single-agent therapies. In the present review, we highlight emerging
information about the redundant and specific functions of PARP-1 and PARP-2 in genome surveillance and DNA repair
pathways. Understanding these roles might provide invaluable clues to design new cancer therapeutic approaches. In addition,
we provide an overview of ongoing clinical trials with PARP inhibitors and the value of PARP-1 and PARP-2 expression as
prognostic biomarkers in cancer. (AJCR0000027).
Keywords: Poly(ADP-ribose) polymerases, poly(ADP-ribosyl)ation, DNA repair, genomic instability, therapeutic approaches,
prognostic markers, cancer
Full Text PDF
Address all correspondence to:
Dr. José Yélamos
Department of Immunology
IMIM-Hospital del Mar
Barcelona Biomedical Research Park (PRBB)
C/ Dr. Aiguader, 88, 08003-Barcelona, Spain.
Tel: +34 93 3160411; Fax: +34 93 3160410
E-mail: jyelamos@imim.es
Review Article
PARP-1 and PARP-2: New players in tumour development
José Yélamos, Jordi Farrés, Laura Llacuna, Coral Ampurdanés, Juan Martin-Caballero
Department of Immunology, Cancer Research Program, IMIM-Hospital del Mar, Barcelona Biomedical Research Park (PRBB),
Barcelona, Spain.
Received December 30, 2010; accepted January 5, 2011; Epub December 6, 2011; Published January 31, 2011
Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 belong to a family of enzymes that, using NAD+ as a substrate,
catalyze poly(ADP-ribosyl)ation of proteins. PARP-1 and PARP-2 catalytic activity is stimulated by DNA-strand breaks targeting
mainly proteins involved in chromatin structure and DNA metabolism, providing strong support for a dual role of both PARP-1
and PARP-2 in the DNA damage response as DNA damage sensors and signal transducers to downstream effectors. The DNA
damage response has important consequences for genomic stability and tumour development. In order to manipulate DNA
damage responses to selectively induce tumour cell death, a considerable effort is centred on defining the molecular
mechanisms that allow cells to detect, respond to, and repair DNA damage. PARP inhibitors that compete with NAD+ at the
highly conserved enzyme active site are arisen as new potential therapeutic strategies as chemo- and radiopotentiation and for
the treatment of cancers with specific DNA repair defects as single-agent therapies. In the present review, we highlight emerging
information about the redundant and specific functions of PARP-1 and PARP-2 in genome surveillance and DNA repair
pathways. Understanding these roles might provide invaluable clues to design new cancer therapeutic approaches. In addition,
we provide an overview of ongoing clinical trials with PARP inhibitors and the value of PARP-1 and PARP-2 expression as
prognostic biomarkers in cancer. (AJCR0000027).
Keywords: Poly(ADP-ribose) polymerases, poly(ADP-ribosyl)ation, DNA repair, genomic instability, therapeutic approaches,
prognostic markers, cancer
Full Text PDF
Address all correspondence to:
Dr. José Yélamos
Department of Immunology
IMIM-Hospital del Mar
Barcelona Biomedical Research Park (PRBB)
C/ Dr. Aiguader, 88, 08003-Barcelona, Spain.
Tel: +34 93 3160411; Fax: +34 93 3160410
E-mail: jyelamos@imim.es
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American Journal of Cancer Research
| ISSN: 2156-6976 |