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Levin DS , McKenna AE , Motycka TA , Matsumoto Y , Tomkinson AE
Interaction between PCNA and DNA ligase I is critical for joining of Okazaki fragments and long-patch base-excision repair
Current Biology. 2000 Jul 27;10(15) :919-922
PMID: ISI:000088979300019   
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Abstract
DNA ligase I belongs to a family of proteins that bind to proliferating cell nuclear antigen (PCNA) via a conserved 8- amino-acid motif [1], Here we examine the biological significance of this interaction. Inactivation of the PCNA- binding site of DNA ligase I had no effect on its catalytic activity or its interaction with DNA polymerase beta, In contrast, the loss of PCNA binding severely compromised the ability of DNA ligase I to join Okazaki fragments. Thus, the interaction between PCNA and DNA ligase 1 is not only critical for the subnuclear targeting of the ligase, but also for coordination of the molecular transactions that occur during lagging-strand synthesis. A functional PCNA-binding site was also required for the ligase to complement hypersensitivity of the DNA ligase I mutant cell line 46BR.1G1 to monofunctional alkylating agents, indicating that a cytotoxic lesion is repaired by a PCNA-dependent DNA repair pathway. Extracts from 46BR.1G1 cells were defective in long-patch, but not short- patch, base-excision repair (BER), Our results show that the interaction between PCNA and DNA ligase I has a key role in long patch ER and provide the first evidence for the biological significance of th is repair mechanism. (C) 2000 Elsevier Science Ltd, All rights reserved.
Notes
Times Cited: 12 English Article 348HK CURR BIOL