Interaction Replication Maps Home   

S phase Mitosis DNA damage Replication inhibition Annotations and References

Annotations for the Replication Interaction Maps

A1 7F ORC, the Origin Recognition Complex, is a complex of 6 subunits. ORC binds chromosomal sites that are capable of initiating DNA replication. In yeast cells, ORC recognizes Autonomous Replicating Sequences (ARS elements) (R1) in an ATP dependent manner (R2). ORC orthologues were found in other eukaryotes, including mammals (R3), but the DNA sequence or structural requirements for mammalian ORC binding had not been elucidated yet. In Drosophila, ORC binds the Chorion gene replication origin, ACE3 (R4).

A2 7F ORC1 associates less tightly than other subunits in the formation of the ORC complex (R5). In Xenopus, it may leave the complex during S-phase (R6)(R7); similar observations suggest that this also happens in mammals (R8)(R9).

A3 6F ORC1 is phosphorylated by Cyclin A and Cyclin B complexes (R10)(R11). ORC1 is ubiquitinated, and released from chromatin during S-phase (R95)

A4 6-7E ORC2,3,4 form a tight complex (R12)(R13). ORC2 and 3 may form a tighter complex that binds ORC4 (R17). The ORC 2,3,4 complex localizes to chromatin depending on E2F in Drosophila (R4). The ORC2-4 complex is hyperphosphorylated on ORC2 at M phase (R14)(R15).

A5 7E ORC5 forms a complex with ORC 2-4 (R12)(R13)(R17). ORC5 directly interacts with cdc6 in yeast (R16).

A6 7E ORC6 probably binds only weakly to the other ORC subunits (R17). The presence of ORC6 in the pre-replication complex depends on E2F, as E2F mutants fail to include the ORC6 in the complex (R18).

A7 7F Two complexes of ORC subunits can bind DNA:ORC1-6 and ORC2-6. In mammalian cells, ORC1 leaves chromatin after initiation of DNA replication. (see interaction 2 for details).

A8 7F ORC2 phosphorylation inhibits initiation of DNA replication (R14)(R15).

A9 4E Cdc6 binds to the ORC:DNA complex at the beginning of G1 and leaves the complex before G1/S (R5). Cdc6 is essential for DNA replication in Xenopus (R19). In S. pombe, initiation of DNA replication depends on the presence of Cdc6 before the end of G1, but not after the activation of Cdks (R20). Cdc6 interacts directly with ORC (R21). In Xenopus, it localizes near origins (R22).

A10 3-4D Cdc6 is phosphorylated primarily by Cyclin A:Cdk2 (R24)(R25) and Cyclin E:Cdk2 (R26). Phosphorylation localizes Cdc6 to the cytoplasm (R27)(R26)(R48); (R45) and probably targets Cdc6 for ubiquitination (R28). Cdc6 binds Cyclin E (R23). Phosphorylated Cdc6 is transported from the nucleus to the cytoplasm, preventing licensing during S-phase (R45).

A11 4E Cdt1 is part of the pre-replication complex (R29). Cdt binding to Pre-RC is essential for loading MCMs to create the pre-replication complex (R29).

A12 4E Cdt1 binding to the ORC complex requires prior binding of Cdc6 to the complex(R29).

A13 4D Geminin binds Cdt1 (R30) and degrades it to prevent loading of MCMs to chromatin (R31).

A14 1E-2G The MCM complex, a helicase, is known as a part of the "licensing" complex (R32). Binding of the MCM complex to the ORC complex on chromatin constitutes the pre-replication complex, which confers competence for initiation of DNA replication. MCMs associate with origin-specific DNA prior to initiation of DNA replication; after replication the association becomes non-specific (R33)(R34). In yeast, MCM-chromatin association depends on Cdc6 (R35)(R36).

A15 1-2F MCM4,6,7, are tightly bound to each other (R44), loosely bound to the other MCM proteins. This complex exhibits helicase activity (Not shown) (R45).

A16 1F MCM4 is phosphorylated by Cyclin B:Cdk1 in Xenopus (R46); and humans (R47) (no clear evidence for the kinase identity in human cells, but the same phosphorylation sites as in Xenopus imply that the kinases are the same). Some phosphorylation activity was observed with Cyclin A:Cdk1 (R87).

A17 2F Phosphorylation of MCM4 reduces the affinity of the MCM complex to chromatin and reduces the helicase activity of the MCM complex (R46).

A18 2G MCM3 forms a tight complex with MCM5 (R41)(R42). MCM3/5 form a looser complex with the other MCM proteins (R43).

A19 2F MCM2 loosely associated with the MCM4, 6,7, complex (R43).

A20 1E MCM2 is a target of phosphorylation by a kinase family that includes cdc7 in yeast and hsk1 in humans (R37)(R38)(R39)(R40)(R26). Phosphorylation facilitates binding of MCM2 to other MCM subunits (see interaction 21).

A21 1E-F MCM2 phosphorylation by cdc7 type kinases (Cdc7:Dbf4 in yeast, hsk/dpf4 in humans) facilitates binding of MCM2 to other MCM subunits and initiation of DNA replication (R37).

A22 2D-3E MCM10 associates with MCM2-7 and chromatin in humans (R75). MCM10 is required for assembly of the pre-replication complex in S. cerevisiae (R79) Xenopus (R99)(R100) and human cells. Binding of MCM10 to chromatin seems to occur throughout the cell cycle (R103)(R104).

A23 4F-G Cdc45 incorporates into the pre-replication complex (R50) and is essential for initiation of DNA replication in yeast. Cdc45 co-immunoprecipitates with MCMs (R51). In yeast, Cdc45 interacts with MCMs (R52) and ORC2 (R50)(R33) and its association with DNA depends on Cdc6 and MCM (R50)(R33). Cdc45 binding to chromatin, but not Cdc45 transcription, requires an active E2F in Drosophila (R97). Chromatin binding is inhibited by the DNA damage checkpoint (R94).

A24 3-4G Binding of Cdc45 to the ORC:MCM complex on chromatin necessitates two kinase complexes: S-phase Cyclin:Cdk, especially Cyclin E:Cdk2, and homologs of yeast Cdc7:Dbf4 (DDK - hsk1 in humans). The yeast homologue of Cylin E:Cdk2 was shown to be required for Cdc45 binding to chromatin in yeast (R50); Cdc7:Dbf4 was shown to be also necessary (R101)(R102). Cdc7:Dbf4 was shown directly to phosphorylate Cdc45.

A25 1A Double stranded breaks inhibit the addition of Cdc45 to the pre-initiation complex (ORC:MCM:Cdc7) in Xenopus extracts. This inhibition depends on the activity of the ATM kinase (R94). ATM dependent activation of MreI:nbs:Rad50 complex can also inhibit progression through S-phase, but this activation does not inhibit binding of Cdc45 to chromatin (R98).

A26 5-6G Cdc45 immunoprecipitates with origin DNA before initiation, but binds non-specifically to DNA after initiation of DNA replication (R33). Cdc45 interacts with DNA polymerase alpha (R53) and hsCdc45 associates with ORC2 (R5).

A27 4F-G MCM10 binds to the chromatin-bound MCM complex and this binding is essential for recruitment of Cdc45 to the pre-initiation complex (R104).

A28 5A-7B Cyclin dependent kinases can phosphorylate various components of the licensing and initiation pathways as a complex with their appropriate cyclin partners.Cyclins are synthesized at specific times during the cell cycle and regulate kinase activities. These interactions are inhibited by phosphorylation of the kinases, which can be relieved by phosphatases of the Cdc25 family (see interaction 43) or by small molecule inhibitors such as p21. (see interactions 29, 30, 33).

A29 6A Cdk2 can bind either Cyclin A or Cyclin E. For details on activation of Cdk2 (R76).

A30 6B Cdc2 (Cdk1), in association with either Cyclin B or Cyclin A, phosphorylates ORC2. Phosphorylation inhibits initiation of DNA replication. Cyclin B:Cdc2 phosphorylates ORC in vitro; probably prevents replication during mitosis (R49). In S. pombe, ORC2 is phosphorylated by Cdc2 (R77) and phosphorylation helps prevent reinitiation (R78). Cyclin A:Cdc2 binds ORC and phosphorylates ORC2p in Xenopus (R83).

A31 4-5C Cyclin B:Cdk1 complexes are mitotic complexes. These kinase complexes phosphorylate MCM4, an inhibitory phosphorylation which reduces binding of the MCM complex to chromatin (R46).

A32 6D Cyclin B1:Cdk1 phosphorylates ORC1 and ORC2 during mitosis (R10)(R11)(R49).

A33 6D-7C The transcription factor p53 facilitates the synthesis of various molecules involved in cellular response to genotoxic conditions. Among others, it facilitates transcription of the cyclin dependent kinase inhibitor p21, gadd45, and molecules involved in apoptosis. For details, see (R76).

A34 6B-7C During interphase, the activity of the Cyclin B:Cdk1 complex is inhibited by the phosphorylation of Cdk1 on Thr 14 and 15 by Wee1 (R92).

A35 3G Cdk2, in combination with its cyclin partners, phosphorylates CDC45 and facilitates its binding to licensed DNA in concert with another phosphorylation mediated by hsk1/dpf4 (R101).

A36 4D Cdk2, in combination with its cyclin partners, phosphorylates Cdc6 and targets it for transport to the cytoplasm and degradation (R24)(R25)(R26)(R45).

A37 6E Cyclin A:Cdk2 phosphorylates ORC1 (R80).

A38 4A Inhibition of DNA replication by the DNA topoisomerase I inhibitor camptothecin, or by UV irradiation activates the ATR - dependent pathway of the S-phase checkpoint (R88).

A39 3A-B CHK2 is phosphorylated after replication arrest by ATR, the homologue of yeast Rad3/Mec1 (R61)(R62)(R63). Rad3/Mec2 is required for phosphorylation of cds1 and phosphorylates cds1 in vitro (R69). In yeast, cds1 is involved in the mitosis checkpoint: regulates phosphorylation of CDKs, Cyclin B:Cdk1 through Wee and Mik (R64)(R65)(R66).

A40 4B Phosphorylation of Wee1 by CHK1 on Ser549 enhances its ability to bind 14-3-3 proteins during interphase (not shown) and increases kinase activity of Wee1 (R93). Kinase activity during interphase guards against premature activation of the mitotic Cyclin:Cdk complexes (e.g. Cyclin B:Cdk1) and prevents mitotic entry as a part of the G2/M checkpoint. For more details on Wee1 interactions see (R76).

A41 3B-C CHK1 phosphorylates Cdc25A in response to DNA damage (R72)(R67).

A42 3C Phosphorylation of Cdc25A leads to its exclusion from the nucleus in yeast (R70)(R72). The phosphorylated protein cannot activate the mitotic Cyclin B:Cdk1 complex (R73)(R74).

A43 7C Cdc25A phosphatase activity is required for activation of Cdks (R90)(R91). CHK2 mediated phosphorylation following irradiation and activation by ATM leads to degradation of Cdc25A (R89).

A44 2A Double strand DNA breaks trigger the signal transduction cascade, whose first step is phosphorylation by the ATM kinase.These phosphorylation steps lead to inhibition of further initiation of DNA replication on licensed DNA by inhibiting the hsk1/dpf4 and the cyclin dependent kinases (see interactions 47-49), and may trigger apoptosis through the p53-mediated pathway (see interaction 50). There is also some evidence that ATM may directly inhibit binding of Cdc45 to licensed chromatin (see interaction 45).

A45 2A ATM may directly inhibit binding of Cdc45 to licensed chromatin through a pathway that does not involve the inhibition Cdc25A to disallow cyclin dependent kinase activity (R89).

A46 2B ATM phosphorylates p53 in response to DNA damage (R85)(R86). This phosphorylation may led to p53-mediated apoptosis. For details see (R76).

A47 1B HScds1/CHK2 is phosphorylated after irradiation and formation of DNA strand breaks, but not after treatment with the drug hydroxyurea (R71)(R58).

A48 2B CHK2 phosphorylates Cdc25A after DNA damage (R67)(R68)(R72)(R67).

A49 1-2C Hsk1/dpf4 is the human orthologue of yeast Cdc7:Dbf4. Cdc7:Dbf4 is required for onset of replication in yeast and for prevention of reassembly of pre-replication complex on origins (R54)(R55)(R56)(R57). Dbf4 is the regulatory protein; its expression levels regulate cdc7 activity (R58). The dbf4 mouse homologue interacts with MCM2 (R59).

A50
1E-2E
Hsk1:dfp1 phosphorylates MCM2 (R38) and Cdc45 (R50).
A51
1D
Binding of MCM10 to dfp1 facilitates kinase activity of hsk1 (R104).
A52
2C
Activation of the S-phase checkpoint in Xenopus inhibits hhsk1:dfp1 kinase activity through a mechanism which requires ATR (R105).
A53
1-2C Auto-phosphorylation of hsk1 inhibits the activity of the hsk1:dfp1 complex (R103).
A54
1D
MCM10 is phosphorylated in G2/M, and this phosphorylation leads to its degradation (R103).
A55
6C
DNA damage or potential genotoxic conditions trigger the signal transduction cascade mediated by the transcription factor p53. For details, see reference (R76).

Literature Cited in Annotations:

R1. Bell, S. P. and Stillman, B.(1992) Nature, 357(6374), 128-34. [PubMed]
R2. Klemm, R. D., Austin, R. J. and Bell, S. P. (1997) Cell, 88(4), 493-502. [PubMed]
R3. Gavin, K. A., Hidaka, M. and Stillman, B. (1995) Science, 270(5242), 1667-71. [PubMed]
R4. Austin, R. J., Orr-Weaver, T. L. and Bell, S. P. (1999) Genes Dev, 13(20), 2639-49. [PubMed]
R5. Saha, P., Chen, J., Thome, K. C., Lawlis, S. J., Hou, Z. H., Hendricks, M., Parvin, J. D. and Dutta, A. (1998) Mol Cell Biol, 18(5), 2758-67. [PubMed]
R6. Rowles, A., Chong, J. P., Brown, L., Howell, M., Evan, G. I. and Blow, J. J. (1996) Cell, 87(2), 287-96. [PubMed]
R7. Natale, D. A., Li, C. J., Sun, W. H. and DePamphilis, M. L. (2000) Embo J, 19(11), 2728-38. [PubMed]
R8. Kreitz, S., Ritzi, M., Baack, M. and Knippers, R. (2001) J Biol Chem, 276(9), 6337-42. [PubMed]
R9. Mendez, J. and Stillman, B. (2000) Mol Cell Biol, 20(22), 8602-12. [PubMed]
R10. Ohtani, K., DeGregori, J., Leone, G., Herendeen, D. R., Kelly, T. J. and Nevins, J. R. (1996) Mol Cell Biol, 16(12), 6977-84. [PubMed]
R11. Wolf, D. A., Wu, D. and McKeon, F. (1996) J Biol Chem, 271(51), 32503-6. [PubMed]
R12. Ishiai, M., Dean, F. B., Okumura, K., Abe, M., Moon, K. Y., Amin, A. A., Kagotani, K., Taguchi, H., Murakami, Y., Hanaoka, F., O'Donnell, M., Hurwitz, J. and Eki, T. (1997) Genomics, 46(2), 294-8. [PubMed]
R13. Quintana, D. G., Hou, Z., Thome, K. C., Hendricks, M., Saha, P. and Dutta, A. (1997) J Biol Chem, 272(45), 28247-51. [PubMed]
R14. Carpenter, P. B., Mueller, P. R. and Dunphy, W. G. (1996) Nature, 379(6563), 357-60. [PubMed]
R15. Carpenter, P. B. and Dunphy, W. G. (1998) J Biol Chem, 273(38), 24891-7. [PubMed]
R16. Liang, C., Weinreich, M. and Stillman, B. (1995) Cell, 81(5), 667-76. [PubMed]
R17. Vashee, S., Simancek, P., Challberg, M. D. and Kelly, T. J. (2001) J Biol Chem, 276(28), 26666-73. [PubMed]
R18. Hateboer, G., Wobst, A., Petersen, B. O., Le Cam, L., Vigo, E., Sardet, C. and Helin, K. (1998) Mol Cell Biol, 18(11), 6679-97. [PubMed]
R19. Williams, R. S., Shohet, R. V. and Stillman, B. (1997) Proc Natl Acad Sci U S A, 94(1), 142-7. [PubMed]
R20. Coleman, T. R., Carpenter, P. B. and Dunphy, W. G. (1996) Cell, 87(1), 53-63. [PubMed]
R21. Bell, S. P., Kobayashi, R. and Stillman, B. (1993) Science, 262(5141), 1844-9. [PubMed]
R22. Romanowski, P., Madine, M. A., Rowles, A., Blow, J. J. and Laskey, R. A. (1996) Curr Biol, 6(11), 1416-25. [PubMed]
R23. Petersen, B. O., Lukas, J., Sorensen, C. S., Bartek, J. and Helin, K. (1999) Embo J, 18(2), 396-410. [PubMed]
R24. Brown, G. W., Jallepalli, P. V., Huneycutt, B. J. and Kelly, T. J. (1997) Proc Natl Acad Sci U S A, 94(12), 6142-7. [PubMed]
R25. Lopez-Girona, A., Mondesert, O., Leatherwood, J. and Russell, P. (1998) Mol Biol Cell, 9(1), 63-73. [PubMed]
R26. Jiang, W., Wells, N. J. and Hunter, T. (1999) Proc Natl Acad Sci U S A, 96(11), 6193-8. [PubMed]
R27 Jallepalli, P. V., Tien, D. and Kelly, T. J. (1998) Proc Natl Acad Sci U S A, 95(14), 8159-64. [PubMed]
R28. Jallepalli, P. V. and Kelly, T. J. (1996) Genes Dev, 10(5), 541-52. [PubMed]
R29. Maiorano, D., Moreau, J. and Mechali, M. (2000) Nature, 404(6778), 622-5. [PubMed]
R30. Wohlschlegel, J. A., Dwyer, B. T., Dhar, S. K., Cvetic, C., Walter, J. C. and Dutta, A. (2000) Science, 290(5500), 2309-12. [PubMed]
R31. McGarry, T. J. and Kirschner, M. W. (1998) Cell, 93(6), 1043-53. [PubMed]
R32. Maine, G. T., Sinha, P. and z, B. K. (1984) Genetics, 106(3), 365-85. [PubMed]
R33. Aparicio, O. M., Weinstein, D. M. and Bell, S. P. (1997) Cell, 91(1), 59-69. [PubMed]
R34. Tanaka, T., Knapp, D. and Nasmyth, K. (1997) Cell, 90(4), 649-60. [PubMed]
R35. Donovan, S., Harwood, J., Drury, L. S. and Diffley, J. F. (1997) Proc Natl Acad Sci U S A, 94(11), 5611-6. [PubMed]
R36. Ogawa, Y., Takahashi, T. and Masukata, H. (1999) Mol Cell Biol, 19(10), 7228-36. [PubMed]
R37. Masai, H., Matsui, E., You, Z., Ishimi, Y., Tamai, K. and Arai, K.(2000). J Biol Chem, 275, 29042-52. [PubMed]
R38. Lei, M., Kawasaki, Y., Young, M. R., Kihara, M., Sugino, A. and Tye, B. K. (1997) Genes Dev, 11(24), 3365-74. [PubMed]
R39. Oshiro, G., Owens, J. C., Shellman, Y., Sclafani, R. A. and Li, J. J. (1999) Mol Cell Biol, 19(7), 4888-96. [PubMed]
R40. Weinreich, M., Liang, C. and Stillman, B. (1999) Proc Natl Acad Sci U S A, 96(2), 441-6. [PubMed]
R41. Kimura, H., Takizawa, N., Nozaki, N. and Sugimoto, K. (1995) Nucleic Acids Res, 23(12), 2097-104. [PubMed]
R42. Schulte, D., Richter, A., Burkhart, R., Musahl, C. and Knippers, R. (1996) Eur J Biochem, 235(1-2), 144-51. [PubMed]
R43. Sherman, D. A., Pasion, S. G. and Forsburg, S. L. (1998) Mol Biol Cell, 9(7), 1833-45. [PubMed]
R44. Musahl, C., Schulte, D., Burkhart, R. and Knippers, R.(1995). Eur J Biochem, 230, 1096-101. [PubMed]
R45. Ishimi, Y., Ichinose, S., Omori, A., Sato, K. and Kimura, H. (1996) J Biol Chem, 271(39), 24115-22. [PubMed]
R46. Hendrickson, M., Madine, M., Dalton, S. and Gautier, J. (1996) Proc Natl Acad Sci U S A, 93(22), 12223-8. [PubMed]
R47. Todorov, I. T., Attaran, A. and Kearsey, S. E. (1995) J Cell Biol, 129(6), 1433-45. [PubMed]
R48. Delmolino, L. M., Saha, P. and Dutta, A. (2001) J Biol Chem, 276, 26947-54. [PubMed]
R49. Kelly, T. J. and Brown, G. W. (2000) Annu Rev Biochem, 69, 829-80. [PubMed]
R50. Zou, L. and Stillman, B. (1998) Science, 280(5363), 593-6. [PubMed]
R51. Hopwood, B. and Dalton, S. (1996) Proc Natl Acad Sci U S A, 93(22), 12309-14. [PubMed]
R52. Hennessy, K. M., Lee, A., Chen, E. and Botstein, D. (1991) Genes Dev, 5(6), 958-69. [PubMed]
R53. Mimura, S. and Takisawa, H. (1998) Embo J, 17(19), 5699-707. [PubMed]
R54. Bousset, K. and Diffley, J. F. (1998) Genes Dev, 12(4), 480-90. [PubMed]
R55. Schwob, E., Bohm, T., Mendenhall, M. D. and Nasmyth, K. (1994) Cell, 79(2), 233-244. [PubMed]
R56. Dahmann, C., Diffley, J. F. and Nasmyth, K. A. (1995) Curr Biol, 5(11), 1257-69. [PubMed]
R57. Piatti, P. M., Monti, L. D., Valsecchi, G., Conti, M., Nasser, R., Guazzini, B., Fochesato, E., Phan, C. V., Pontiroli, A. E. and Pozza, G. (1996) Circulation, 94(11), 2703-7. [PubMed]
R58. Brown, A. L., Lee, C. H., Schwarz, J. K., Mitiku, N., Piwnica-Worms, H. and Chung, J. H. (1999) Proc Natl Acad Sci U S A, 96(7), 3745-50. [PubMed]
R59. Lepke, M., Putter, V., Staib, C., Kneissl, M., Berger, C., Hoehn, K., Nanda, I., Schmid, M. and Grummt, F. (1999) Mol Gen Genet, 262(2), 220-9. [PubMed]
R60. Cheng, L., Collyer, T. and Hardy, C. F. (1999) Mol Cell Biol, 19(6), 4270-8. [PubMed]
R61. Boddy, M. N., Furnari, B., Mondesert, O. and Russell, P. (1998) Science, 280(5365), 909-12. [PubMed]
R62. Sun, Z., Fay, D. S., Marini, F., Foiani, M. and Stern, D. F. (1996) Genes Dev, 10(4), 395-406. [PubMed]
R63. Lindsay, H. D., Griffiths, D. J., Edwards, R. J., Christensen, P. U., Murray, J. M., Osman, F., Walworth, N. and Carr, A. M. (1998) Genes Dev, 12(3), 382-95. [PubMed]
R64. Enoch, T. and Nurse, P. (1990) Cell, 60(4), 665-73. [PubMed]
R65. Rhind, N. and Russell, P. (1998) Genetics, 149(4), 1729-37. [PubMed]
R66. Lundgren, K., Walworth, N., Booher, R., Dembski, M., Kirschner, M. and Beach, D. (1991) Cell, 64(6), 1111-22. [PubMed]
R67. Furnari, B., Blasina, A., Boddy, M. N., McGowan, C. H. and Russell, P. (1999) Mol Biol Cell, 10(4), 833-45. [PubMed]
R68. Ford, J. C., al-Khodairy, F., Fotou, E., Sheldrick, K. S., Griffiths, D. J. and Carr, A. M. (1994) Science, 265(5171), 533-5. [PubMed]
R69. Martinho, R. G., Lindsay, H. D., Flaggs, G., DeMaggio, A. J., Hoekstra, M. F., Carr, A. M. and Bentley, N. J. (1998) Embo J, 17(24), 7239-49. [PubMed]
R70. Zeng, Y., Forbes, K. C., Wu, Z., Moreno, S., Piwnica-Worms, H. and Enoch, T. (1998) Nature, 395(6701), 507-10. [PubMed]
R71. Matsuoka, S., Huang, M. and Elledge, S. J. (1998) Science, 282(5395), 1893-7. [PubMed]
R72. Peng, C. Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S. and Piwnica-Worms, H. (1997) Science, 277(5331), 1501-5. [PubMed]
R73. Lopez-Girona, A., Furnari, B., Mondesert, O. and Russell, P. (1999) Nature, 397(6715), 172-5. [PubMed]
R74. Zeng, Y. and Piwnica-Worms, H. (1999) Mol Cell Biol, 19(11), 7410-9. [PubMed]
R75. Izumi, M., Yanagi, K., Mizuno, T., Yokoi, M., Kawasaki, Y., Moon, K. Y., Hurwitz, J., Yatagai, F. and Hanaoka, F. (2000) Nucleic Acids Res, 28, 4769-77. [PubMed]
R76. http://discover.nci.nih.gov/kohnk/interaction_maps.html
R77. Lygerou, Z. and Nurse, P.(1999) J Cell Sci, 112, 3703-12. [PubMed]
R78. Vas, A., Mok, W. and Leatherwood, J. (2001) Mol Cell Biol, 21, 5767-77. [PubMed]
R79. Homesley, L., Lei, M., Kawasaki, Y., Sawyer, S., Christensen, T. and Tye, B. K. (2000) Genes Dev, 14, 913-26. [PubMed]
R80. Findeisen, M., El-Denary, M., Kapitza, T., Graf, R. and Strausfeld, U. (1999) Eur J Biochem, 264, 415-26. [PubMed]
R81. Tatsumi, Y., Tsurimoto, T., Shirahige, K., Yoshikawa, H. and Obuse, C. (2000) J Biol Chem, 275, 5904-10. [PubMed]
R82. Thome, K. C., Dhar, S. K., Quintana, D. G., Delmolino, L., Shahsafaei, A. and Dutta, A. (2000) J Biol Chem, 275, 35233-41. [PubMed]
R83. Romanowski, P., Marr, J., Madine, M. A., Rowles, A., Blow, J. J., Gautier, J. and Laskey, R. A. (2000) J Biol Chem, 275, 4239-43. [PubMed]
R84. Strausfeld, U. P., Howell, M., Rempel, R., Maller, J. L., Hunt, T. and Blow, J. J. (1994) Curr Biol, 4, 876-83. [PubMed]
R85. Banin, S., Moyal, L., Shieh, S., Taya, Y., Anderson, C. W., Chessa, L., Smorodinsky, N. I., Prives, C., Reiss, Y., Shiloh, Y., and Ziv, Y. (1998) Science, 281, 1674-1677. [PubMed]
R86. Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S. Y., Taya, Y., Prives, C., and Abraham, R. T. (1999) Genes Dev, 13, 152-157. [PubMed]
R87. Ishimi, Y., Komamura-Kohno, Y., You, Z., Omori, A. and Kitagawa, M.(2000) J Biol Chem, 275, 16235-41. [PubMed]
R88. Guo, Z., Kumagai, A., Wang, S. X. and Dunphy, W. G. (2000) Genes Dev, 14, 2745-56. [PubMed]
R89. Falck, J., Mailand, N., Syljuasen, R. G., Bartek, J. and Lukas, J. (2001) Nature, 410, 842-7. [PubMed]
R90. Hoffmann, I., Draetta, G. and Karsenti, E. (1994) EMBO J, 13, 4302-10. [PubMed]
R91. Jinno, S., Suto, K., Nagata, A., Igarashi, M., Kanaoka, Y., Nojima, H. and Okayama, H.(1994) EMBO J, 13, 1549-56. [PubMed]
R92. Parker, L. L. and Piwnica-Worms, H. (1992) Science, 257, 1955-7. [PubMed]
R93. Lee, J., Kumagai, A., Dunphy, W. G.(2001) Mol Biol Cell, 12, 551-63. [PubMed]
R94. Costanzo, V., Robertson, K., Ying, C. Y., Kim, E., Avvedimento, E., Gottesman, M., Grieco, D. and Gautier, J. (2000) Mol Cell, 6, 649-59. [PubMed]
R95. Li, C. J. and DePamphilis, M. L. (2002) Mol Cell Biol, 22, 105-16. [PubMed]
R96. Wohlschlegel, J. A., Dhar, S. K., Prokhorova, T. A., Dutta, A. and Walter, J. C. (2002) Mol Cell, 9, 233-40. [PubMed]
R97. Arata, Y., Fujita, M., Ohtani, K., Kijima, S. and Kato, J.Y. (2000) J Biol Chem, 275, 6337-45. [PubMed]
R98. Falck, J., Petrini, J. H., Williams, B. R., Lukas, J. and Bartek, J. (2002) Nat Genet, 30, 290 - 294. [PubMed]
R99. Walter, J.C. (2000) J Biol Chem, 275, 39773-8. [PubMed]
R100. Jares, P. and Blow, J. J. (2000) Genes Dev, 14, 1528-40. [PubMed]
R101. Nougarede, R., Della Seta, F., Zarzov, P. and Schwob, E. (2000) Mol Cell Biol, 20, 3795-806. [PubMed]
R102. Zou, L. and Stillman, B.(2000) Mol Cell Biol, 20, 3086-96. [PubMed]
R103.
Izumi, M., Yatagai, F. and Hanaoka, F. (2001) J Biol Chem, 276, 48526-31. [PubMed]
R104.
Lee, J. K., Seo, Y. S. and Hurwitz, J. (2003) Proc Natl Acad Sci U S A, 100, 2334-9. [PubMed]
R105.
Costanzo, V., Shechter, D., Lupardus, P. J., Cimprich, K. A., Gottesman, M. and Gautier, J. (2003) Mol Cell, 11, 203-13. [PubMed]

featured by Dr. M. Aladjem aladjemm@mail.nih.gov and Stefania Pasa pasa@cba.unige.it