The N‐terminal domain of human DNA ligase I contains the nuclear localization signal and directs the enzyme to sites of DNA replication

DNA replication in mammalian cells occurs in discrete nuclear foci called ‘replication factories’. Here we show that DNA ligase I, the main DNA ligase activity in proliferating cells, associates with the factories during S phase but displays a diffuse nucleoplasmic distribution in non‐S phase nuclei...

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Bibliographic Details
Published in:The EMBO journal 1995-11, Vol.14 (21), p.5379-5386
Main Authors: Montecucco, A., Savini, E., Weighardt, F., Rossi, R., Ciarrocchi, G., Villa, A., Biamonti, G.
Format: Article
Language:English
Subjects:
3T3 Cells
Amino Acid Sequence
Animals
Base Sequence
Cell Cycle
Cell Nucleus - enzymology
DNA Ligase ATP
DNA Ligases - chemistry
DNA Ligases - metabolism
DNA Replication
HeLa Cells
Humans
Mice
Molecular Sequence Data
Sequence Analysis
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Summary:DNA replication in mammalian cells occurs in discrete nuclear foci called ‘replication factories’. Here we show that DNA ligase I, the main DNA ligase activity in proliferating cells, associates with the factories during S phase but displays a diffuse nucleoplasmic distribution in non‐S phase nuclei. Immunolocalization analysis of both chloramphenicol acetyltransferase (CAT)‐DNA ligase I fusion proteins and epitope tagged DNA ligase I mutants allowed the identification of a 13 amino acid functional nuclear localization signal (NLS) located in the N‐terminal regulatory domain of the protein. Furthermore, the NLS is immediately preceded by a 115 amino acid region required for the association of the enzyme with the replication factories. We propose that in vivo the activity of DNA ligase I could be modulated through the control of its sub‐nuclear compartmentalization.
ISSN:0261-4189
1460-2075
DOI:10.1002/j.1460-2075.1995.tb00222.x