Early Embryonic Lethality Due to Targeted Inactivation of DNA Ligase III

作者: Nahum Puebla-Osorio , Devin B. Lacey , Frederick W. Alt , Chengming Zhu

DOI: 10.1128/MCB.26.10.3935-3941.2006

关键词:

摘要: DNA ligases catalyze the joining of strand breaks in phosphodiester backbone duplex and play essential roles replication, recombination, repair, maintenance genomic integrity. Three mammalian ligase genes have been identified, their corresponding distinct metabolism. III is proposed to be involved repairing single-strand breaks, but its precise role has not yet demonstrated directly. To determine cellular growth, embryonic development, we introduced targeted interruption (LIG3) gene into mouse. Mice homozygous for LIG3 disruption showed early lethality. We found that mutant developmental process stops at 8.5 days postcoitum (dpc), excessive cell death occurs 9.5 dpc. cells relatively normal XRCC1 levels elevated sister chromatid exchange. These findings indicate repair activities required development therefore cannot replaced by other ligases.

参考文章(56)
Alan E Tomkinson, Ling Chen, Zhiwan Dong, John B Leppard, David S Levin, Zachary B Mackey, Teresa A Motycka, Completion of base excision repair by mammalian DNA ligases Progress in Nucleic Acid Research and Molecular Biology. ,vol. 68, pp. 151- 164 ,(2001) , 10.1016/S0079-6603(01)68097-8
H Teraoka, T Sumikawa, K Tsukada, Purification of DNA ligase II from calf thymus and preparation of rabbit antibody against calf thymus DNA ligase II. Journal of Biological Chemistry. ,vol. 261, pp. 6888- 6892 ,(1986) , 10.1016/S0021-9258(19)62699-2
Ulf Grawunder, Matthias Wilm, Xiantuo Wu, Peter Kulesza, Thomas E Wilson, Matthias Mann, Michael R Lieber, None, Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells Nature. ,vol. 388, pp. 492- 495 ,(1997) , 10.1038/41358
Y. Kubota, R. A. Nash, A. Klungland, P. Schär, D. E. Barnes, T. Lindahl, Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. The EMBO Journal. ,vol. 15, pp. 6662- 6670 ,(1996) , 10.1002/J.1460-2075.1996.TB01056.X
Intisar Husain, Alan E. Tomkinson, William A. Burkhart, Mary B. Moyer, William Ramos, Zachary B. Mackey, Jeffrey M. Besterman, Jingwen Chen, Purification and characterization of DNA ligase III from bovine testes. Homology with DNA ligase II and vaccinia DNA ligase. Journal of Biological Chemistry. ,vol. 270, pp. 9683- 9690 ,(1995) , 10.1074/JBC.270.16.9683
Y.C. Wang, W.A. Burkhart, Z.B. Mackey, M.B. Moyer, W Ramos, I Husain, J Chen, J.M. Besterman, A.E. Tomkinson, Mammalian DNA ligase II is highly homologous with vaccinia DNA ligase. Identification of the DNA ligase II active site for enzyme-adenylate formation. Journal of Biological Chemistry. ,vol. 269, pp. 31923- 31928 ,(1994) , 10.1016/S0021-9258(18)31783-6
Karen M. Frank, JoAnn M. Sekiguchi, Katherine J. Seidl, Wojciech Swat, Gary A. Rathbun, Hwei-Ling Cheng, Laurie Davidson, Landy Kangaloo, Frederick W. Alt, Late embryonic lethality and impaired V(D)J recombination in mice lacking DNA ligase IV. Nature. ,vol. 396, pp. 173- 177 ,(1998) , 10.1038/24172
Bancinyane L. Sibanda, Susan E. Critchlow, Jake Begun, Xue Y. Pei, Stephen P. Jackson, Tom L. Blundell, Luca Pellegrini, Crystal structure of an Xrcc4–DNA ligase IV complex Nature Structural & Molecular Biology. ,vol. 8, pp. 1015- 1019 ,(2001) , 10.1038/NSB725