Posttranscriptional modification of nuclear proteins by poly(ADP-ribosyl)ation in response to DNA strand breaks plays an important role in DNA repair, regulation of apoptosis, and maintenance of genomic stability. A 113-kDa human poly(ADP-ribose) polymerase (PARP) has previously been identified and cloned. However, there is evidence that additional enzymes with PARP activity exist in mammalian cells. I have identified and cloned the cDNAs of two novel approximately 60-kDa human proteins that are 40 and 31% identical to the catalytic C-terminal domain of PARP. These proteins, named PARP-2 and PARP-3, lack the DNA-binding and automodification domains. PARP-2 and PARP-3 mRNAs were detected in 16 different human tissues as major bands of 2.0 and 2.2 kb, respectively. Radiation hybrid analysis assigned the PARP-2 gene (HGMW-approved symbol ADPRTL2) to chromosome 14q11.2-q12 and the PARP-3 gene (HGMW-approved symbol ADPRTL3) to 3p21.1-p22.2. This report shows the existence of a human PARP gene family with at least three closely related members.
Copyright 1999 Academic Press.