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DNA ligase I is recruited to sites of DNA replication by an interaction with proliferating cell nuclear antigen: identification of a common targeting mechanism for the assembly of replication factories
Author(s) -
Montecucco Alessandra,
Rossi Rossella,
Levin David S,
Gary Ronald,
Park Min S,
Motycka Teresa A,
Ciarrocchi Giovanni,
Villa Antonello,
Biamonti Giuseppe,
Tomkinson Alan E
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.13.3786
Subject(s) - replication factor c , dna ligase , biology , dna replication , proliferating cell nuclear antigen , origin recognition complex , control of chromosome duplication , dna clamp , eukaryotic dna replication , replication protein a , dna polymerase delta , microbiology and biotechnology , dna polymerase , processivity , dna , genetics , dna binding protein , reverse transcriptase , transcription factor , gene , polymerase chain reaction
In mammalian cells, DNA replication occurs at discrete nuclear sites termed replication factories. Here we demonstrate that DNA ligase I and the large subunit of replication factor C (RF‐C p140) have a homologous sequence of ∼20 amino acids at their N‐termini that functions as a replication factory targeting sequence (RFTS). This motif consists of two boxes: box 1 contains the sequence IxxFF whereas box 2 is rich in positively charged residues. N‐terminal fragments of DNA ligase I and the RF‐C large subunit that contain the RFTS both interact with proliferating cell nuclear antigen (PCNA) in vitro . Moreover, the RFTS of DNA ligase I and of the RF‐C large subunit is necessary and sufficient for the interaction with PCNA. Both subnuclear targeting and PCNA binding by the DNA ligase I RFTS are abolished by replacement of the adjacent phenylalanine residues within box 1. Since sequences similar to the RFTS/PCNA‐binding motif have been identified in other DNA replication enzymes and in p21 CIP1/WAF1 , we propose that, in addition to functioning as a DNA polymerase processivity factor, PCNA plays a central role in the recruitment and stable association of DNA replication proteins at replication factories.