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CDC9  -  DNA ligase (ATP) CDC9

Saccharomyces cerevisiae S288c

Synonyms: DNA ligase 1, DNA ligase I, YDL164C
 
 
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Disease relevance of CDC9

  • Mutational analysis of Escherichia coli DNA ligase identifies amino acids required for nick-ligation in vitro and for in vivo complementation of the growth of yeast cells deleted for CDC9 and LIG4 [1].
  • Chlorella virus DNA ligase is the smallest eukaryotic ATP-dependent DNA ligase known; it suffices for yeast cell growth in lieu of the essential yeast DNA ligase Cdc9 [2].
 

High impact information on CDC9

  • Saccharomyces cerevisiae cell cycle mutant cdc9 is defective in DNA ligase [3].
  • Insertion of a 20-bp fragment from the CDC9 promoter (containing a MluI element) upstream of LacZ confers both periodic expression and transcriptional induction in cycloheximide following release from cdc28ts arrest [4].
  • To ascertain which sites represented starts for leading or lagging strands, we characterized DNA replication from ARS1 in a cdc9 (DNA ligase I) mutant, defective for joining Okazaki fragments [5].
  • The level of CDC9 transcript increases many fold in late G1 reaching a peak at about the G1/S phase boundary and preceding the peak in histone message by some 20 min [6].
  • This sequence has been shown to be essential for periodic expression of the POL1, CDC9, and TMP1 genes [7].
 

Biological context of CDC9

 

Anatomical context of CDC9

  • Approximately 2.5 +/- 0.07 and 5.7 +/- 0.6 single-strand breaks per 10(8) daltons were detected in DNAs from either CDC9 or cdc9-9 cells converted to spheroplasts immediately after 10 and 25 krads of irradiation, respectively [11].
  • At the restrictive temperature, cell cycle progression of cdc9 cells is blocked sometime after the DNA chain elongation step, whereas cdc9 rad9 delta cells do not arrest at this point and undergo one or two additional divisions [12].
 

Associations of CDC9 with chemical compounds

  • Those genes susceptible to giving rise to formamide-sensitive alleles include the structural gene for DNA ligase, CDC9, and the structural gene for arginine permease, CAN1 [13].
  • Conditional ligase-deficient mutants of Saccharomyces cerevisiae were more sensitive than their parental (CDC9) strain to dose-dependent killing by bleomycin, even when mutant cells were pregrown and exposed to the antibiotic at permissive temperatures [14].
  • We found that yng2 mutants are specifically sensitized to DNA damage in S phase induced by cdc8 or cdc9 mutations, hydroxyurea, camptothecin, or methylmethane sulfonate (MMS) [15].
  • Our studies with the rad9 delta mutation show that RAD9 plays a role in the cell cycle arrest of methyl methanesulfonate-treated cells and is absolutely required for the cell cycle arrest in the temperature-sensitive cdc9 mutant, which is defective in DNA ligase [12].
  • cdc9, a temperature-sensitive mutant defective in polynucleotide deoxyribonucleic acid (DNA) ligase activity, accumulates low-molecular-weight DNA fragments (as measured by sedimentation of DNA in alkaline sucrose gradients) at the nonpermissive temperature after irradiation with ultraviolet light [16].
 

Other interactions of CDC9

  • For the CDC21, CDC9, and POL1 genes, the Mlu I site has been shown to be absolutely required for periodic transcription [17].
  • A similar loss of cell cycle-dependent transcription was noted for two of the three remaining histone loci, while the HO and CDC9 genes continued to be expressed periodically [18].
  • The CDC9 gene of Saccharomyces cerevisiae encodes a DNA ligase, and we have determined the nucleotide sequence of a 3.85 kb fragment of DNA which encompasses the convergently transcribed CDC9 and CDC36 genes [10].
  • Differential display analysis demonstrated that the expression of cell cycle genes encoding DNA ligase (CDC9) and histone acetyltransferase (HAT2) was strongly repressed in FOH-treated cells [19].
  • Furthermore, using a cdc9 mutant to trap incision intermediates, we demonstrate that rad7 and rad16 mutants are proficient in NER-dependent DNA incision in vivo [20].
 

Analytical, diagnostic and therapeutic context of CDC9

References

  1. Mutational analysis of Escherichia coli DNA ligase identifies amino acids required for nick-ligation in vitro and for in vivo complementation of the growth of yeast cells deleted for CDC9 and LIG4. Sriskanda, V., Schwer, B., Ho, C.K., Shuman, S. Nucleic Acids Res. (1999) [Pubmed]
  2. Analysis of the DNA joining repertoire of Chlorella virus DNA ligase and a new crystal structure of the ligase-adenylate intermediate. Odell, M., Malinina, L., Sriskanda, V., Teplova, M., Shuman, S. Nucleic Acids Res. (2003) [Pubmed]
  3. Saccharomyces cerevisiae cell cycle mutant cdc9 is defective in DNA ligase. Johnston, L.H., Nasmyth, K.A. Nature (1978) [Pubmed]
  4. Direct induction of G1-specific transcripts following reactivation of the Cdc28 kinase in the absence of de novo protein synthesis. Marini, N.J., Reed, S.I. Genes Dev. (1992) [Pubmed]
  5. Chromosomal ARS1 has a single leading strand start site. Bielinsky, A.K., Gerbi, S.A. Mol. Cell (1999) [Pubmed]
  6. Periodic transcription as a means of regulating gene expression during the cell cycle: contrasting modes of expression of DNA ligase genes in budding and fission yeast. White, J.H., Barker, D.G., Nurse, P., Johnston, L.H. EMBO J. (1986) [Pubmed]
  7. Regulation of the yeast DNA replication genes through the Mlu I cell cycle box is dependent on SWI6. Verma, R., Smiley, J., Andrews, B., Campbell, J.L. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  8. The yeast CDC9 gene encodes both a nuclear and a mitochondrial form of DNA ligase I. Willer, M., Rainey, M., Pullen, T., Stirling, C.J. Curr. Biol. (1999) [Pubmed]
  9. DNA ligase I from Saccharomyces cerevisiae: physical and biochemical characterization of the CDC9 gene product. Tomkinson, A.E., Tappe, N.J., Friedberg, E.C. Biochemistry (1992) [Pubmed]
  10. The nucleotide sequence of the DNA ligase gene (CDC9) from Saccharomyces cerevisiae: a gene which is cell-cycle regulated and induced in response to DNA damage. Barker, D.G., White, J.H., Johnston, L.H. Nucleic Acids Res. (1985) [Pubmed]
  11. Ligase-deficient yeast cells exhibit defective DNA rejoining and enhanced gamma ray sensitivity. Moore, C.W. J. Bacteriol. (1982) [Pubmed]
  12. Cloning and sequence analysis of the Saccharomyces cerevisiae RAD9 gene and further evidence that its product is required for cell cycle arrest induced by DNA damage. Schiestl, R.H., Reynolds, P., Prakash, S., Prakash, L. Mol. Cell. Biol. (1989) [Pubmed]
  13. Formamide sensitivity: a novel conditional phenotype in yeast. Aguilera, A. Genetics (1994) [Pubmed]
  14. cdc9 ligase-defective mutants of Saccharomyces cerevisiae exhibit lowered resistance to lethal effects of bleomycin. Moore, C.W. J. Bacteriol. (1982) [Pubmed]
  15. NuA4 subunit Yng2 function in intra-S-phase DNA damage response. Choy, J.S., Kron, S.J. Mol. Cell. Biol. (2002) [Pubmed]
  16. Incision and postincision steps of pyrimidine dimer removal in excision-defective mutants of Saccharomyces cerevisiae. Wilcox, D.R., Prakash, L. J. Bacteriol. (1981) [Pubmed]
  17. Identification and purification of a factor that binds to the Mlu I cell cycle box of yeast DNA replication genes. Verma, R., Patapoutian, A., Gordon, C.B., Campbell, J.L. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  18. Trans-acting regulatory mutations that alter transcription of Saccharomyces cerevisiae histone genes. Osley, M.A., Lycan, D. Mol. Cell. Biol. (1987) [Pubmed]
  19. Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism. Machida, K., Tanaka, T., Yano, Y., Otani, S., Taniguchi, M. Microbiology (Reading, Engl.) (1999) [Pubmed]
  20. The yeast RAD7 and RAD16 genes are required for postincision events during nucleotide excision repair. In vitro and in vivo studies with rad7 and rad16 mutants and purification of a Rad7/Rad16-containing protein complex. Reed, S.H., You, Z., Friedberg, E.C. J. Biol. Chem. (1998) [Pubmed]
  21. DNA ligation during excision repair in yeast cell-free extracts is specifically catalyzed by the CDC9 gene product. Wu, X., Braithwaite, E., Wang, Z. Biochemistry (1999) [Pubmed]
  22. Bleomycin-induced DNA repair by Saccharomyces cerevisiae ATP-dependent polydeoxyribonucleotide ligase. Moore, C.W. J. Bacteriol. (1988) [Pubmed]
 
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