DNA ligase I

 

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

 

 

Synonyms

 

ScCdc9, SpCdc17

 

Molecular weight

Sc 85 kDa

 

Mammals

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

Biochemical properties

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

Motifs

•Nuclear replication foci localisation signals (2)

 

Interactions

 

Mammals

• 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)

 

Modifications

•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)

Structure

•Crystal structure (8)

 

Cellular location and expression

 

Other comments

Sc

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

 

Mammals

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

 

Archael

•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.