Sld2

 

Functions in initiation of replication. Key substrate of CDK, phosphorylation promotes interaction with Dpb11, required for initiation of replication in S. cerevisiae  (1) (2)

 

Synonyms

•DRC1 (SC) (3)

•SpDrc1 Noguchi cb 12 599 (2);

•RecQ4/RecQL4 in vertebrates may be orthologue as it has some homology but also has additional recQ related domains (4) (5)

Molecular weight

 

Biochemical properties

 

Motifs

Sc

•Cdk sites (6) (7)

• dephosphorylated by cdc14 (8)

Sp

•Cdc2 sites

 

Protein interactions

Sc

•Dpb11 (3) (9) (direct) (6) (1) (2)  

 

Sp

•Cdc13/cig2 (10)

•Cut5 through BRCT domains (10)

 

Xl

•Cut5  (5)

Modifications

•Phosphorylation (6) (1) (2)

 

Structure

 

Cellular location and expression

 

Other comments

Sp

• order loading relative to GINS, sld3 cdc45 (11)

 

Xl

•Associates with chromatin after pre-RC formation. Required for chromatin association of replicative DNA polymerases (4) (5)

•essential for replication in extracts (4)

 

Mammals

• recQ4 involved in Rothmann-Thompson syndrome (4)

• possible involvement in repair (12)

Revised by

 

Last edited

13 April 08

 

 

1.    Zegerman,P. and Diffley,J.F. (2007) Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature 445, 281-285.

2.    Tanaka,S., Umemori,T., Hirai,K., Muramatsu,S., Kamimura,Y. and Araki,H. (2007) CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Nature 445, 328-332.

3.    Wang,H. and Elledge,S.J. (1999) DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 96, 3824-3829.

4.    Sangrithi,M.N., Bernal,J.A., Madine,M., Philpott,A., Lee,J., Dunphy,W.G. and Venkitaraman,A.R. (2005) Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome. Cell 121, 887-898.

5.    Matsuno,K., Kumano,M., Kubota,Y., Hashimoto,Y. and Takisawa,H. (2006) The N-terminal noncatalytic region of Xenopus RecQ4 is required for chromatin binding of DNA polymerase alpha in the initiation of DNA replication. Mol Cell Biol 26, 4843-4852.

6.    Masumoto,H., Muramatsu,S., Kamimura,Y. and Araki,H. (2002) S-Cdk-dependent phosphorylation of Sld2 essential for chromosomal DNA replication in budding yeast. Nature 415, 651-655.

7.    Tak,Y.S., Tanaka,Y., Endo,S., Kamimura,Y. and Araki,H. (2006) A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11. EMBO J 25, 1987-1996.

8.    Bloom,J. and Cross,F.R. (2007) Novel role for Cdc14 sequestration: Cdc14 dephosphorylates factors that promote DNA replication. Mol Cell Biol 27, 842-853.

9.    Kamimura,Y., Masumoto,H., Sugino,A. and Araki,H. (1998) Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Mol Cell Biol 18, 6102-6109.

10.  Noguchi,E., Shanahan,P., Noguchi,C. and Russell,P. (2002) CDK phosphorylation of Drc1 regulates DNA replication in fission yeast. Curr Biol 12, 599-605.

11.  Yabuuchi,H., Yamada,Y., Uchida,T., Sunathvanichkul,T., Nakagawa,T. and Masukata,H. (2006) Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins. EMBO J 25, 4663-4674.

12.  Kumata,Y., Tada,S., Yamanada,Y., Tsuyama,T., Kobayashi,T., Dong,Y.P., Ikegami,K., Murofushi,H., Seki,M. and Enomoto,T. (2007) Possible involvement of RecQL4 in the repair of double-strand DNA breaks in Xenopus egg extracts. Biochim Biophys Acta 1773, 556-564.