Csm3/Swi3/Tipin
Component of Tof1(swi1/Tim)-Mrc1 (claspin)-Csm3(Swi3/Tipin) replication pausing checkpoint complex
Synonyms |
Sc -Csm3 /Sp-Swi3/mammals- tipin |
Molecular weight |
36.3 kDa (Sc) |
Biochemical properties |
|
Motifs |
|
Protein interactions |
Sc •Mcm7 (1) •Tof1 stoichiometric / Mrc1 substoichiometric in hu block (1) • Synthetic lethality pol a (1) • in GINS complex (2) • Peroxiredoxin prxd2 (oxygen scavenger) (3)
Sp • SAP1 (needed for chromatin recruitment) (4)
Mammals • MCM (5) MCM7 (6) • Tim (5) all through the cycle and co dependent for stability and localization (7) , (6) • rpa (34kDa subunit) (3) •cyclin E ( as substrate) (6) • claspin (6) • polymerase (6) |
Modifications |
|
Structure |
|
Cellular location and expression |
Sc •Part of replisome progression complex (2)
Mammals • levels rise throughout S (3) • same loading kinetics as MCM7 (6)
|
Other comments |
Sc •Needed for RFB (8) • 1 of 2 parallel pathways of sister chromatid cohesion (other is mrc1 ctf18 ctf8 and dcc1) (9) • role in replication termination (10)
Sp •Required for pausing at mating type locus (11) (12) (13) • role in sister chromatid cohesion (14)
Mammals • needed for chk1 phosphorylation and nuclear accumulation claspin on replication stress (7) • suggested role in stopping fork collapse (6) , (15)
|
Revised by |
|
Last edited |
14 April 08 |
1. Nedelcheva,M.N., Roguev,A., Dolapchiev,L.B., Shevchenko,A., Taskov,H.B., Shevchenko,A., Stewart,A.F. and Stoynov,S.S. (2005) Uncoupling of unwinding from DNA synthesis implies regulation of MCM helicase by Tof1/Mrc1/Csm3 checkpoint complex. J Mol Biol 347, 509-521.
2. Gambus,A., Jones,R.C., Sanchez-Diaz,A., Kanemaki,M., van Deursen,F., Edmondson,R.D. and Labib,K. (2006) GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat Cell Biol 8, 358-366.
3. Gotter,A.L., Suppa,C. and Emanuel,B.S. (2007) Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors. J Mol Biol 366, 36-52.
4. Noguchi,C. and Noguchi,E. (2007) Sap1 promotes the association of the replication fork protection complex with chromatin and is involved in the replication checkpoint in Schizosaccharomyces pombe. Genetics 175, 553-566.
5. Chou,D.M. and Elledge,S.J. (2006) Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function. Proc Natl Acad Sci U S A 103, 18143-18147.
6. Errico,A., Costanzo,V. and Hunt,T. (2007) Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts. Proc Natl Acad Sci U S A 104, 14929-14934.
7. Yoshizawa-Sugata,N. and Masai,H. (2007) Human Tim/Timeless-interacting protein, Tipin, is required for efficient progression of S phase and DNA replication checkpoint. J Biol Chem 282, 2729-2740.
8. Calzada,A., Hodgson,B., Kanemaki,M., Bueno,A. and Labib,K. (2005) Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA replication fork. Genes Dev 19, 1905-1919.
9. Xu,H., Boone,C. and Brown,G.W. (2007) Genetic dissection of parallel sister-chromatid cohesion pathways. Genetics 176, 1417-1429.
10. Mohanty,B.K., Bairwa,N.K. and Bastia,D. (2006) The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 103, 897-902.
11. Dalgaard,J.Z. and Klar,A.J. (2000) swi1 and swi3 perform imprinting, pausing, and termination of DNA replication in S. pombe. Cell 102, 745-751.
12. Krings,G. and Bastia,D. (2004) swi1- and swi3-dependent and independent replication fork arrest at the ribosomal DNA of Schizosaccharomyces pombe. Proc Natl Acad Sci U S A 101, 14085-14090.
13. Nedelcheva-Veleva,M.N., Krastev,D.B. and Stoynov,S.S. (2006) Coordination of DNA synthesis and replicative unwinding by the S-phase checkpoint pathways. Nucleic Acids Res 34, 4138-4146.
14. Ansbach,A.B., Noguchi,C., Klansek,I.W., Heidlebaugh,M., Nakamura,T.M. and Noguchi,E. (2008) RFCCtf18 and the Swi1-Swi3 Complex Function in Separate and Redundant Pathways Required for the Stabilization of Replication Forks to Facilitate Sister Chromatid Cohesion in Schizosaccharomyces pombe. Mol Biol Cell 19, 595-607.
15. Unsal-Kacmaz,K., Chastain,P.D., Qu,P.P., Minoo,P., Cordeiro-Stone,M., Sancar,A. and Kaufmann,W.K. (2007) The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement. Mol Cell Biol 27, 3131-3142.