The nuclear protein PH5P of the inter-alpha-inhibitor superfamily: a missing link between poly(ADP-ribose)polymerase and the inter-alpha-inhibitor family and a novel actor of DNA repair?

Poly(ADP-ribose)polymerase is a nuclear NAD-dependent enzyme and an essenti al nick sensor involved in cellular processes where nicking and rejoining o f DNA strands are required. The inter-alpha-inhibitor family is comprized o f several plasma proteins that all harbor one or more so-called heavy chain s designated H1-H4. The latter originate from precursor polypeptides H1P-H4 P whose upper two thirds are highly homologous. We now describe a novel pro tein that includes (i) a so-called BRCT domain found in many proteins invol ved in DNA repair, (ii) an area that is homologous to the NAD-dependent cat alytic domain of poly(ADP-ribose)polymerase, (iii) an area that is homologo us to the upper two thirds of precursor polypeptides H1P-H4P and (iv) a pro line-rich region with a potential nuclear localization signal. This protein now designated PH5P points to as yet unsuspected links between poly(ADP-ri bose)polymerase and the inter-alpha-inhibitor family and is likely to be in volved in DNA repair. (C) 1999 Federation of European Biochemical Societies .