Premium
The N‐terminal domain of human DNA ligase I contains the nuclear localization signal and directs the enzyme to sites of DNA replication.
Author(s) -
Montecucco A.,
Savini E.,
Weighardt F.,
Rossi R.,
Ciarrocchi G.,
Villa A.,
Biamonti G.
Publication year - 1995
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 - 10.1002/j.1460-2075.1995.tb00222.x
Subject(s) - biology , dna ligase , dna replication , genetics , dna ligases , dna , eukaryotic dna replication , seqa protein domain , microbiology and biotechnology , computational biology
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.