Single-particle analysis of full-length human poly(ADP-ribose) polymerase 1

• Main Authors: Kenichi Kouyama, Kouta Mayanagi, Setsu Nakae, Yoshisuke Nishi, Masanao Miwa, Tsuyoshi Shirai
• Format: Article
• Language: English
• Published: The Biophysical Society of Japan 2019-02-01
• Series: Biophysics and Physicobiology
• Subjects: parp1; dna repair; electron microscopy; structural biology
• Online Access: https://doi.org/10.2142/biophysico.16.0_59

PolyADP-ribosylation (PARylation) is a posttranslational modification that is involved in the various cellular functions including DNA repair, genomic stability, and transcriptional regulation. PARylation is catalyzed by the poly(ADP-ribose) polymerase (PARP) family proteins, which mainly recognize damaged DNA and initiate repair processes. PARP inhibitors are expected to be novel anticancer drugs for breast and ovarian cancers having mutation in BRCA tumor suppressor genes. However the structure of intact (full-length) PARP is not yet known. We have produced and purified the full-length human PARP1 (h-PARP1), which is the major family member of PARPs, and analyzed it with single particle electron microscopy. The electron microscopic images and the reconstructed 3D density map revealed a dimeric configuration of the h-PARP1, in which two ring-shaped subunits are associated with two-fold symmetry. Although the PARP1 is hypothesized to form a dimer on damaged DNA, the quaternary structure of this protein is still controversial. The present result would provide the first structural evidence of the dimeric structure of PARP1.