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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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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.
Times Cited: 12 English Article 348HK CURR BIOL