Quick Poll results from the August Issue of OncoFacts 2009
What does poly ADP-ribose polymerase, member 1 (PARP 1) do?
| Down-regulates the estrogen receptor, making breast cancer cells appear “triple-negative” |
 |
0.00% |
|
| Interferes with function of the “normal” BRCA-1 gene in BRCA mutants |
|
20.00% |
|
| Repairs single-stranded DNA breaks |
|
40.00% |
|
| Repairs double-stranded DNA breaks |
|
40.00% |
|
PARP is a protein involved in many cellular processes including DNA repair and programmed cell death. There are 17 members of the PARP family, all with different structures and functions. The PARP inhibitors have reached the clinic, and one of the most important functions of PARP is the repair of single-strand DNA breaks or “nicks”. PARP binds to sites with these nicks and recruits SRCC1, DNA ligase III, and DNA polymerase beta to the site to begin the repair. This binding and recruitment are called “base excision repair” or BER. If one inhibits PARP1, there is the inability to repair single-stranded breaks, the replication fork stalls, and double strand breaks accumulate. These double-strand breaks, however, are repaired by a mechanism called homologous recombination. However, BRCA1 and BRCA 2 are necessary for the homologous recombination pathway to function. Thus, recently reported clinical trials have shown remarkable response rates in advanced cancers that are BRCA 1 or 2 mutants with the PARP inhibitors.
* The aggregate results from this question were compiled from the responses submitted by oncologists who participated in the OncoFacts Quick Poll monthly question.