The family of Poly (ADP-ribose) polymerases (PARP) is constituted by enzymes involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death. The PARP family comprises 17 members, with slight differences in structure and functions. PARP is composed of four domains of interest: a DNA-binding domain, a caspase-cleaved domain (see below), an auto-modification domain, and a catalytic domain. The catalytic domain is responsible for Poly (ADP-ribose) polymerization. This domain has a highly conserved motif that is common to all members of the PARP family. The formation of PAR polymer is similar to the formation of DNA polymer from nucleoside triphosphates.
A substantial body of preclinical and clinical data has accumulated with PARP inhibitors in various forms of cancer. In this context, the role of PARP in single-strand DNA break repair is relevant, leading to replication-associated lesions that cannot be repaired if homologous recombination repair (HRR) is defective, and leading to the synthetic lethality of PARP inhibitors in HRR-defective cancer. HRR defects are classically associated with BRCA1 and 2 mutations associated with familial breast and ovarian cancer, but there may be many other causes of HRR defects. Thus, PARP inhibitors of various types (e.g. olaparib) for BRCA mutant breast and ovarian cancers can extend beyond these tumors. Here you can see a recent crystal structure of human PARP15 (PDB code: 7OTF)
#molecularart ... #immolecular ... #PARP ... #inhibitor ... #cancer ... #DNArepair ... #xray
PARP15 structure rendered with @proteinimaging and finally depicted with @corelphotopaint
A substantial body of preclinical and clinical data has accumulated with PARP inhibitors in various forms of cancer. In this context, the role of PARP in single-strand DNA break repair is relevant, leading to replication-associated lesions that cannot be repaired if homologous recombination repair (HRR) is defective, and leading to the synthetic lethality of PARP inhibitors in HRR-defective cancer. HRR defects are classically associated with BRCA1 and 2 mutations associated with familial breast and ovarian cancer, but there may be many other causes of HRR defects. Thus, PARP inhibitors of various types (e.g. olaparib) for BRCA mutant breast and ovarian cancers can extend beyond these tumors. Here you can see a recent crystal structure of human PARP15 (PDB code: 7OTF)
#molecularart ... #immolecular ... #PARP ... #inhibitor ... #cancer ... #DNArepair ... #xray
PARP15 structure rendered with @proteinimaging and finally depicted with @corelphotopaint
