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PMID:11125146

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Citation

Wohlschlegel, JA, Dwyer, BT, Dhar, SK, Cvetic, C, Walter, JC and Dutta, A (2000) Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290:2309-12

Abstract

In all eukaryotic organisms, inappropriate firing of replication origins during the G2 phase of the cell cycle is suppressed by cyclin-dependent kinases. Multicellular eukaryotes contain a second putative inhibitor of re-replication called geminin. Geminin is believed to block binding of the mini-chromosome maintenance (MCM) complex to origins of replication, but the mechanism of this inhibition is unclear. Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading. The inhibition of DNA replication by geminin that is observed in cell-free DNA replication extracts is reversed by the addition of excess Cdt1. In the normal cell cycle, Cdt1 is present only in G1 and S, whereas geminin is present in S and G2 phases of the cell cycle. Together, these results suggest that geminin inhibits inappropriate origin firing by targeting Cdt1.

Links

PubMed Online version:10.1126/science.290.5500.2309

Keywords

Amino Acid Sequence; Animals; Cell Cycle Proteins/chemistry; Cell Cycle Proteins/metabolism; Cell Cycle Proteins/pharmacology; Cell Nucleus/metabolism; Cell-Free System; Chromatin/metabolism; DNA Replication; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/pharmacology; Evolution, Molecular; G1 Phase; G2 Phase; HeLa Cells; Humans; Interphase; Molecular Sequence Data; Molecular Weight; Precipitin Tests; Recombinant Fusion Proteins/metabolism; Replication Origin; S Phase; Xenopus

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GEMI

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H211

F

Seeded From UniProt

complete

HUMAN:GEMI

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9I9A7

F

Seeded From UniProt

complete

HUMAN:GEMI

involved_in

GO:0035563: positive regulation of chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:Q91628)

Seeded From UniProt

complete

XENLA:MCM4B

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

XENLA:MCM4A

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

XENLA:ORC2

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CDT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75496

F

Seeded From UniProt

complete

HUMAN:CDT1

involved_in

GO:0035563: positive regulation of chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P30664)
  • has_input:(UniProtKB:Q5XK83)
  • has_input:(UniProtKB:Q91628)

Seeded From UniProt

complete

HUMAN:CDT1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:CDT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75496

F

Seeded From UniProt

complete

HUMAN:GEMI

involved_in

GO:0071163: DNA replication preinitiation complex assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GEMI

involved_in

GO:2000104: negative regulation of DNA-dependent DNA replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GEMI

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GEMI

GO:0008156: negative regulation of DNA replication

ECO:0000314:

P

Fig.3

complete

HUMAN:GEMI

involved_in

GO:0035563: positive regulation of chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:Q91628)

Seeded From UniProt

complete

HUMAN:CDT1

involved_in

GO:2001178: positive regulation of mediator complex assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDT1

involved_in

GO:2000105: positive regulation of DNA-dependent DNA replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDT1

involved_in

GO:0071163: DNA replication preinitiation complex assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDT1

involved_in

GO:0030174: regulation of DNA-dependent DNA replication initiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDT1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CDT1

involved_in

GO:0035563: positive regulation of chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_regulation_target:(UniProtKB:P30664)
  • has_regulation_target:(UniProtKB:Q5XK83)
  • has_regulation_target:(UniProtKB:Q91628)

Seeded From UniProt

complete

HUMAN:CDT1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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