title: A DDB2 mutant protein unable to interact with PCNA promotes cell cycle progression of human transformed embryonic kidney cells.
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 is not known. In this study, we have addressed this question by using HEK293 cell clones stably expressing DDB2(Wt) protein, or a mutant form (DDB2(Mut)) unable to interact with PCNA. We report that overexpression of the DDB2(Mut) 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 p21(CDKN1A) protein level, and a shorter cell cycle length, has been observed in the DDB2(Mut) cells. These results suggest that DDB2 influences cell cycle progression thanks to its interaction with PCNA.
authors.affiliation: a Dipartimento di Medicina Molecolare ; Unità di Immunologia e Patologia generale; Università di Pavia ; Pavia , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Perucca
authors.affiliation: a Dipartimento di Medicina Molecolare ; Unità di Immunologia e Patologia generale; Università di Pavia ; Pavia , Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sommatis
authors.affiliation: a Dipartimento di Medicina Molecolare ; Unità di Immunologia e Patologia generale; Università di Pavia ; Pavia , Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mocchi
authors.affiliation: b Istituto di Genetica Molecolare (IGM) del CNR ; Pavia , Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: Prosperi
authors.affiliation: a Dipartimento di Medicina Molecolare ; Unità di Immunologia e Patologia generale; Università di Pavia ; Pavia , Italy.
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Stivala
authors.affiliation: a Dipartimento di Medicina Molecolare ; Unità di Immunologia e Patologia generale; Università di Pavia ; Pavia , Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Cazzalini
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D020741:rho GTP-Binding Proteins
keywords: DDB2; DNA replication, PCNA; cell cycle; tumor growth