PARP Inhibitors For Breast, Ovarian And Other Cancers

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The recently analyzed evolutionary history of the poly(ADP-ribose)polymerase (PARP) found these proteins in eukaryotes, a wide range of organisms - animals, plants, molds, fungi, algae and protozoa - whose cells contain complex structures enclosed within membranes. While PARP proteins can be found with any of these groups, they have been most extensively studied in mammals.

In these organisms, PARPs have key functions in DNA repair, genome integrity and epigenetic regulation. More recently it has been found that proteins within the PARP family have a broader range of functions that initially predicted.

Researchers used computers to identify 236 PARP proteins from 77 species across five of the six groups, and performed extensive phylogenetic analyses of the identified PARP regions.

PARPs are found in all eukaryotic groups for which sequence is available, but some individual lineages within groups have independently lost these genes. The PARP family can be subdivided into six branches or clades. Two of these clades were likely found in the last common eukaryotic ancestor. In addition, they have identified PARPs in organisms in which they have not previously been described.

Three main conclusions were drawn from the study:

First, the broad distribution and pattern of representation of PARP genes indicated to the researchers that the ancestor of all existing eukaryotes encoded proteins of this type.

Second, the ancestral PARP proteins had different functions and activities. One of these proteins likely functioned in DNA damage response.

Third, the diversity of the PARP family is larger than previously documented, suggesting as more eukaryotic genomes become available, this gene family will grow in both number and type.

Source: The study, "Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes," was authored by Rebecca S. Lamb, PhD, an assistant professor of Molecular Genetics and Ohio State University colleagues Matteo Citarelli and Sachin Teotia and appeared in an issue of the journal BMC Evolutionary Biology. The work was supported by a grant from the Ohio Plant Biotechnology Consortium and by funds from the Ohio State University.