6xty

Structural highlights

Disease

[MCM4_HUMAN] Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency. The disease is caused by mutations affecting the gene represented in this entry. [MCM5_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.

Function

[MCM7_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for S-phase checkpoint activation upon UV-induced damage.^{[1] [2] [3]} [CDC45_HUMAN] Required for initiation of chromosomal DNA replication. [MCM4_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.^{[4] [5]} [PSF1_HUMAN] The GINS complex plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex seems to bind preferentially to single-stranded DNA. GINS1 is essential for function.^[6] [PSF3_HUMAN] The GINS complex plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex seems to bind preferentially to single-stranded DNA.^[7] [WDHD1_HUMAN] Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication.^[8] [MCM3_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for DNA replication and cell proliferation. [PSF2_HUMAN] The GINS complex plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex seems to bind preferentially to single-stranded DNA.^[9] [MCM2_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division.^[10] [MCM5_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (By similarity). Interacts with MCMBP. [SLD5_HUMAN] The GINS complex plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS4 is important for GINS complex assembly. GINS complex seems to bind preferentially to single-stranded DNA.^[11] [MCM6_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.^[12]

References

1. ↑ Cortez D, Glick G, Elledge SJ. Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10078-83. doi:, 10.1073/pnas.0403410101. Epub 2004 Jun 21. PMID:15210935 doi:http://dx.doi.org/10.1073/pnas.0403410101
2. ↑ Tsao CC, Geisen C, Abraham RT. Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling. EMBO J. 2004 Nov 24;23(23):4660-9. Epub 2004 Nov 11. PMID:15538388 doi:http://dx.doi.org/7600463
3. ↑ Ishimi Y. A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. J Biol Chem. 1997 Sep 26;272(39):24508-13. PMID:9305914
4. ↑ Tsuji T, Ficarro SB, Jiang W. Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells. Mol Biol Cell. 2006 Oct;17(10):4459-72. doi: 10.1091/mbc.e06-03-0241. Epub 2006, Aug 9. PMID:16899510 doi:http://dx.doi.org/10.1091/mbc.e06-03-0241
5. ↑ Ishimi Y. A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. J Biol Chem. 1997 Sep 26;272(39):24508-13. PMID:9305914
6. ↑ Kamada K, Kubota Y, Arata T, Shindo Y, Hanaoka F. Structure of the human GINS complex and its assembly and functional interface in replication initiation. Nat Struct Mol Biol. 2007 May;14(5):388-96. Epub 2007 Apr 8. PMID:17417653 doi:10.1038/nsmb1231
7. ↑ Kamada K, Kubota Y, Arata T, Shindo Y, Hanaoka F. Structure of the human GINS complex and its assembly and functional interface in replication initiation. Nat Struct Mol Biol. 2007 May;14(5):388-96. Epub 2007 Apr 8. PMID:17417653 doi:10.1038/nsmb1231
8. ↑ Im JS, Ki SH, Farina A, Jung DS, Hurwitz J, Lee JK. Assembly of the Cdc45-Mcm2-7-GINS complex in human cells requires the Ctf4/And-1, RecQL4, and Mcm10 proteins. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15628-32. Epub 2009 Sep 8. PMID:19805216 doi:http://dx.doi.org/0908039106
9. ↑ Kamada K, Kubota Y, Arata T, Shindo Y, Hanaoka F. Structure of the human GINS complex and its assembly and functional interface in replication initiation. Nat Struct Mol Biol. 2007 May;14(5):388-96. Epub 2007 Apr 8. PMID:17417653 doi:10.1038/nsmb1231
10. ↑ Todorov IT, Pepperkok R, Philipova RN, Kearsey SE, Ansorge W, Werner D. A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division. J Cell Sci. 1994 Jan;107 ( Pt 1):253-65. PMID:8175912
11. ↑ Kamada K, Kubota Y, Arata T, Shindo Y, Hanaoka F. Structure of the human GINS complex and its assembly and functional interface in replication initiation. Nat Struct Mol Biol. 2007 May;14(5):388-96. Epub 2007 Apr 8. PMID:17417653 doi:10.1038/nsmb1231
12. ↑ Ishimi Y. A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. J Biol Chem. 1997 Sep 26;272(39):24508-13. PMID:9305914
13. ↑ Rzechorzek NJ, Hardwick SW, Jatikusumo VA, Chirgadze DY, Pellegrini L. CryoEM structures of human CMG-ATPgammaS-DNA and CMG-AND-1 complexes. Nucleic Acids Res. 2020 May 26. pii: 5846034. doi: 10.1093/nar/gkaa429. PMID:32453425 doi:http://dx.doi.org/10.1093/nar/gkaa429