UV-induced binding of ING1 to PCNA regulates the induction of apoptosis

Previous studies have shown that UV-induced binding of p21(WAF1) to PCNA th rough the PCNA-interacting protein (PIP) domain in p21(WAF1) promotes a swi tch from DNA replication to DNA repair by altering the PCNA protein complex . Here we show that the p33(ING1b) isoform of the ING1 candidate tumour sup pressor contains a PIP domain. UV rapidly induces p33(ING1b) to bind PCNA c ompetitively through this domain, a motif also found in DNA ligase, the DNA repair-associated FEN1 and XPG exo/endonucleases, and DNA methyltransferas e. Interaction of p33(ING1b) with PCNA occurs between a significant proport ion of ING1 and PCNA, increases more than tenfold in response to UV and is specifically inhibited by overexpression of p21(WAF1), but not by p16(MTS1) , which has no PIP sequence. In contrast to wild-type p33(ING1b), ING1 PIP mutants that do not bind PCNA do not induce apoptosis, but protect cells fr om UV-induced apoptosis, suggesting a role for this PCNA-p33(ING1b) interac tion in eliminating UV-damaged cells through programmed cell death. These d ata indicate that ING1 competitively binds PCNA through a site used by grow th regulatory and DNA damage proteins, and may contribute to regulating the switch from DNA replication to DNA repair by altering the composition of t he PCNA protein complex.