title: The human DNA polymerase lambda interacts with PCNA through a domain important for DNA primer binding and the interaction is inhibited by p21/WAF1/CIP1.
abstract: In this paper we show that DNA polymerase lambda (pol lambda) interacts with proliferating cell nuclear antigen (PCNA) in vivo in human cells. Moreover, by using recombinant mutated PCNA, we could demonstrate that pol lambda interacts with both the interdomain-connecting loop and the nearby hydrophobic pocket on the anterior of PCNA and that critical residues within a helix-hairpin-helix domain of pol lambda, important for proper DNA primer binding, are also involved in the enzyme's interaction with PCNA. Finally, we show that the tumor suppressor protein p21(WAF1/CIP1) can efficiently compete in vitro with pol lambda for binding to PCNA. Given the high rate of frameshift mutations induced by pol lambda and its ability to bypass abasic sites, accurate regulation of pol lambda activity by PCNA and p21 concerted action might be important for preventing genetic instability.
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy. maga@igm.cnr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Blanca
authors.forename: Igor
authors.initials: I
authors.lastname: Shevelev
authors.forename: Isabelle
authors.initials: I
authors.lastname: Frouin
authors.forename: Kristijan
authors.initials: K
authors.lastname: Ramadan
authors.forename: Silvio
authors.initials: S
authors.lastname: Spadari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villani
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hübscher
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D018809:Proliferating Cell Nuclear Antigen; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta