PMID- 10637286
OWN - NLM
STAT- MEDLINE
DCOM- 20000407
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 11
IP  - 1
DP  - 2000 Jan
TI  - Regulation of mitotic inhibitor Mik1 helps to enforce the DNA damage checkpoint.
PG  - 1-11
AB  - The protein kinase Chk1 enforces the DNA damage checkpoint. This checkpoint
      delays mitosis until damaged DNA is repaired. Chk1 regulates the activity and
      localization of Cdc25, the tyrosine phosphatase that activates the cdk Cdc2. Here
      we report that Mik1, a tyrosine kinase that inhibits Cdc2, is positively
      regulated by the DNA damage checkpoint. Mik1 is required for checkpoint response 
      in strains that lack Cdc25. Long-term DNA damage checkpoint arrest fails in
      Deltamik1 cells. DNA damage increases Mik1 abundance in a Chk1-dependent manner. 
      Ubiquitinated Mik1 accumulates in a proteasome mutant, which indicates that Mik1 
      normally has a short half-life. Thus, the DNA damage checkpoint might regulate
      Mik1 degradation. Mik1 protein and mRNA oscillate during the unperturbed cell
      cycle, with peak amounts detected around S phase. These data indicate that
      regulation of Mik1 abundance helps to couple mitotic onset to the completion of
      DNA replication and repair. Coordinated negative regulation of Cdc25 and positive
      regulation of Mik1 ensure the effective operation of the DNA damage checkpoint.
FAU - Baber-Furnari, B A
AU  - Baber-Furnari BA
AD  - Departments of Molecular Biology and Cell Biology, The Scripps Research
      Institute, La Jolla, California 92037, USA.
FAU - Rhind, N
AU  - Rhind N
FAU - Boddy, M N
AU  - Boddy MN
FAU - Shanahan, P
AU  - Shanahan P
FAU - Lopez-Girona, A
AU  - Lopez-Girona A
FAU - Russell, P
AU  - Russell P
LA  - eng
GR  - F32 GM018503/GM/NIGMS NIH HHS/United States
GR  - F32 GM018503-03/GM/NIGMS NIH HHS/United States
GR  - R01 CA077325/CA/NCI NIH HHS/United States
GR  - CA77325/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA, Fungal)
RN  - 0 (Fungal Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Schizosaccharomyces pombe Proteins)
RN  - 0 (Ubiquitins)
RN  - 0 (ras-GRF1)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (mik1 protein, S pombe)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Checkpoint Kinase 1)
RN  - EC 2.7.11.1 (Chk1 protein, S pombe)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - CDC2 Protein Kinase/metabolism
MH  - Cell Cycle
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cell Nucleus/metabolism
MH  - Checkpoint Kinase 1
MH  - Cysteine Endopeptidases
MH  - *DNA Damage
MH  - DNA Replication
MH  - DNA, Fungal/biosynthesis
MH  - Fungal Proteins/genetics/metabolism
MH  - G2 Phase
MH  - Glutathione Transferase/genetics/metabolism
MH  - Mitosis
MH  - Multienzyme Complexes
MH  - Mutagenesis
MH  - Proteasome Endopeptidase Complex
MH  - Protein Kinases/genetics/metabolism
MH  - Protein-Tyrosine Kinases/genetics/*metabolism/physiology
MH  - RNA, Messenger
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Schizosaccharomyces
MH  - *Schizosaccharomyces pombe Proteins
MH  - *Signal Transduction
MH  - Ubiquitins/metabolism
MH  - ras-GRF1/genetics/metabolism
PMC - PMC14752
EDAT- 2000/01/19 00:00
MHDA- 2000/01/19 00:01
CRDT- 2000/01/19 00:00
PHST- 2000/01/19 00:00 [pubmed]
PHST- 2000/01/19 00:01 [medline]
PHST- 2000/01/19 00:00 [entrez]
AID - 10.1091/mbc.11.1.1 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2000 Jan;11(1):1-11. doi: 10.1091/mbc.11.1.1.