DNA damage binding protein 2 (DDB2) is a protein involved in the early step of DNA damage recognition of the nucleotide excision repair (NER) process. Recently, it has been suggested that DDB2 may play a role in DNA replication, based on its ability to promote cell proliferation. We have previously shown that DDB2 binds PCNA during NER, but also in the absence of DNA damage; however, whether and how this interaction influences cell proliferation in not known. In this study, we have addressed this question by using HEK293 cell clones stably expressing DDB2Wt protein, or a mutant form (DDB2Mut) unable to interact with PCNA. We report that overexpression of the DDB2Mut protein provides a proliferative advantage over the wild type form, by influencing cell cycle progression. In particular, an increase in the number of S-phase cells, together with a reduction in p21CDKN1A protein level, and a shorter cell cycle length, has been observed in the DDB2Mut cells. These results suggest that DDB2 influences cell cycle progression thanks to its interaction with PCNA.
A DDB2 mutant protein unable to interact with PCNA promotes cell cycle progression of human transformed embryonic kidney cells
PERUCCA, PAOLA;SOMMATIS, SABRINA;MOCCHI, ROBERTO;PROSPERI, ENNIO;STIVALA, LUCIA ANNA;CAZZALINI, ORNELLA
2015-01-01
Abstract
DNA damage binding protein 2 (DDB2) is a protein involved in the early step of DNA damage recognition of the nucleotide excision repair (NER) process. Recently, it has been suggested that DDB2 may play a role in DNA replication, based on its ability to promote cell proliferation. We have previously shown that DDB2 binds PCNA during NER, but also in the absence of DNA damage; however, whether and how this interaction influences cell proliferation in not known. In this study, we have addressed this question by using HEK293 cell clones stably expressing DDB2Wt protein, or a mutant form (DDB2Mut) unable to interact with PCNA. We report that overexpression of the DDB2Mut protein provides a proliferative advantage over the wild type form, by influencing cell cycle progression. In particular, an increase in the number of S-phase cells, together with a reduction in p21CDKN1A protein level, and a shorter cell cycle length, has been observed in the DDB2Mut cells. These results suggest that DDB2 influences cell cycle progression thanks to its interaction with PCNA.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
