Identification of a novel, widespread, and functionally important PCNA-binding motif.
Numerous proteins, many essential for the DNA replication machinery, interact with proliferating cell nuclear antigen (PCNA) through the PCNA-interacting peptide (PIP) sequence called the PIP box. We have previously shown that the oxidative demethylase human AlkB homologue 2 (hABH2) colocalizes with PCNA in replication foci. In this study, we show that hABH2 interacts with a posttranslationally modified PCNA via a novel PCNA-interacting motif, which we term AlkB homologue 2 PCNA-interacting motif (APIM). We identify APIM in >200 other proteins involved in DNA maintenance, transcription, and cell cycle regulation, and verify a functional APIM in five of these. Expression of an APIM peptide increases the cellular sensitivity to several cytostatic agents not accounted for by perturbing only the hABH2-PCNA interaction. Thus, APIM is likely to mediate PCNA binding in many proteins involved in DNA repair and cell cycle control during genotoxic stress.
Gilljam
Karin M
KM
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
Feyzi
Emadoldin
E
Aas
Per A
PA
Sousa
Mirta M L
MM
Müller
Rebekka
R
Vågbø
Cathrine B
CB
Catterall
Tara C
TC
Liabakk
Nina B
NB
Slupphaug
Geir
G
Drabløs
Finn
F
Krokan
Hans E
HE
Otterlei
Marit
M
D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; D020816:Amino Acid Motifs / Q000235:genetics*; D000818:Animals; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; D019473:Transcription Factors, TFII; D049308:Dioxygenases; C486440:ALKBH2 protein, human; D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; D004250:DNA Topoisomerases, Type II; D045643:DNA Repair Enzymes