DNA ligase I


Joins Okazaki fragments during DNA replication. Ligase activity also needed for DNA repair and recombination.





ScCdc9, SpCdc17


Molecular weight

Sc 85 kDa



• 102 runs 120 (high proline content) (1)

Biochemical properties

Joins 3’OH to 5’ P in ATP dependent reaction


•Nuclear replication foci localisation signals (2)





• PCNA (3) (4) (needs interaction to process okazaki fragments effectively, probably needed for loading on rather than catalytic activity) (5)

• rad17and each 9-1-1-subunit (6)



•Phosphorylation (CK2) lo g1, up s , peaks g2  off at start g1 (7) In vitro phosphorylation activates ligase – can also be activated by removing of the c terminal inhibitory domain (as topoII)


•Crystal structure (8)


Cellular location and expression


Other comments


• contains other DNA ligases (9) but Cdc9 is involved in DNA replication.



•Four ligases; DNA ligase I most homologous to ScCdc9. (10) (11)



•ligase from thermophile (12)

Revised by


Last edited

13 April 08



1.    Prigent,C., Lasko,D.D., Kodama,K., Woodgett,J.R. and Lindahl,T. (1992) Activation of mammalian DNA ligase I through phosphorylation by casein kinase II. EMBO J 11, 2925-2933.

2.    Cardoso,M.C., Joseph,C., Rahn,H.P., Reusch,R., Nadal-Ginard,B. and Leonhardt,H. (1997) Mapping and use of a sequence that targets DNA ligase I to sites of DNA replication in vivo. J Cell Biol 139, 579-587.

3.    Levin,D.S., Bai,W., Yao,N., O'Donnell,M. and Tomkinson,A.E. (1997) An interaction between DNA ligase I and proliferating cell nuclear antigen: implications for Okazaki fragment synthesis and joining. Proc Natl Acad Sci U S A 94, 12863-12868.

4.    Montecucco,A., Rossi,R., Levin,D.S., Gary,R., Park,M.S., Motycka,T.A., Ciarrocchi,G., Villa,A., Biamonti,G. and Tomkinson,A.E. (1998) DNA ligase I is recruited to sites of DNA replication by an interaction with proliferating cell nuclear antigen: identification of a common targeting mechanism for the assembly of replication factories. EMBO J 17, 3786-3795.

5.    Levin,D.S., Vijayakumar,S., Liu,X., Bermudez,V.P., Hurwitz,J. and Tomkinson,A.E. (2004) A conserved interaction between the replicative clamp loader and DNA ligase in eukaryotes: implications for Okazaki fragment joining. J Biol Chem 279, 55196-55201.

6.    Song,W., Levin,D.S., Varkey,J., Post,S., Bermudez,V.P., Hurwitz,J. and Tomkinson,A.E. (2007) A conserved physical and functional interaction between the cell cycle checkpoint clamp loader and DNA ligase I of eukaryotes. J Biol Chem 282, 22721-22730.

7.    Rossi,R., Villa,A., Negri,C., Scovassi,I., Ciarrocchi,G., Biamonti,G. and Montecucco,A. (1999) The replication factory targeting sequence/PCNA-binding site is required in G(1) to control the phosphorylation status of DNA ligase I. EMBO J 18, 5745-5754.

8.    Pascal,J.M., O'Brien,P.J., Tomkinson,A.E. and Ellenberger,T. (2004) Human DNA ligase I completely encircles and partially unwinds nicked DNA. Nature 432, 473-478.

9.    Teo,S.H. and Jackson,S.P. (1997) Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double-strand break repair. EMBO J 16, 4788-4795.

10.  Lindahl,T. and Barnes,D.E. (1992) Mammalian DNA ligases. Annu Rev Biochem 61, 251-281.

11.  Wei,Y.F., Robins,P., Carter,K., Caldecott,K., Pappin,D.J., Yu,G.L., Wang,R.P., Shell,B.K., Nash,R.A., Schar,P. and et,a. (1995) Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. Mol Cell Biol 15, 3206-3216.

12.  Pascal,J.M., Tsodikov,O.V., Hura,G.L., Song,W., Cotner,E.A., Classen,S., Tomkinson,A.E., Tainer,J.A. and Ellenberger,T. (2006) A flexible interface between DNA ligase and PCNA supports conformational switching and efficient ligation of DNA. Mol Cell 24, 279-291.