Sunday, 18 June 2017

PARP (poly-[adenosine diphosphate-ribose] polymerase)

Poly-(ADP)-ribose polymerase is «a family of proteins involved in a number of cellular processes involving mainly DNA [deoxyribonucleic acid] repair and programmed cell death. The PARP family comprises 17 members (10 putative). They have all very different structures and functions in the cell. One important function of PARP is assisting in the repair of single-strand DNA breaks [1]». It is «a SSB [single-strand break] detector protein» [2].
«Drugs which inhibit (...) PARP (...) are particularly effective in tumors with HR [homologous recombination] deficiencies, such as breast tumors with BCRA1 or BCRA2 [breast cancer 1 or 2] deficiencies. (...) probably (...) PARP inhibitors suppress SSB repair, resulting in greater numbers of unrepaired SSBs, which therefore have a greater chance of hitting a replication fork. Under normal circumstances, the resulting DSB [double-strand break] would be repaired by HR, so the absence or reduction of this backup pathway leads to a substantial increase in DSBs and thus cellular lethality [2].»
Bibliographic references:
[1] Tortora, G., Bergmann, L., Lindh, M., Cervantes-Ruiperez, A., Dziadziuszko, R., Eckhardt, S., Lenz, H., Normanno, N., Perez, D., Scarpa, A., Syrigos, K., Tabernero, J. and Troiani, T. (2014). ESMO glossary in molecular biology of cancer. Viganello-Lugano, Switzerland: European Society for Medical Oncology, p.127.
[2] Joiner, M. and Kogel, A. (2009). Basic clinical radiobiology. 1st ed. Boca Raton, Florida: CRC Press, p.24.

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