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Activation of mammalian DNA ligase I through phosphorylation by casein kinase II.
Author(s) -
Prigent C.,
Lasko D.D.,
Kodama K.,
Woodgett J.R.,
Lindahl T.
Publication year - 1992
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.1460-2075.1992.tb05362.x
Subject(s) - biology , dna ligase , phosphorylation , ubiquitin ligase , casein kinase 2 , casein kinase 1 , microbiology and biotechnology , biochemistry , dna ligases , dna , genetics , protein kinase a , ubiquitin , cyclin dependent kinase 2 , gene
Mammalian DNA ligase I has been shown to be a phosphoprotein. Dephosphorylation of purified DNA ligase I causes inactivation, an effect dependent on the presence of the N‐terminal region of the protein. Expression of full‐length human DNA ligase I in Escherichia coli yielded soluble but catalytically inactive enzyme whereas an N‐terminally truncated form expressed activity. Incubation of the full‐length preparation from E. coli with purified casein kinase II (CKII) resulted in phosphorylation of the N‐terminal region and was accompanied by activation of the DNA ligase. Of a variety of purified protein kinases tested, only CKII stimulated the activity of calf thymus DNA ligase I. Tryptic phosphopeptide analysis of DNA ligase I revealed that CKII specifically phosphorylated a major peptide also apparently phosphorylated in cells, implying that CKII is a protein kinase acting on DNA ligase I in the cell nucleus. These data suggest that DNA ligase I is negatively regulated by its N‐terminal region and that this inhibition can be relieved by post‐translational modification.