PMID- 10617473
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20211203
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 286
IP  - 5449
DP  - 1999 Dec 24
TI  - Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.
PG  - 2528-31
AB  - The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2
      checkpoint kinases, whose activation in response to DNA damage prevents cellular 
      entry into mitosis. Here, it is shown that heterozygous germ line mutations in
      hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype
      usually associated with inherited mutations in the TP53 gene. These observations 
      suggest that hCHK2 is a tumor suppressor gene conferring predisposition to
      sarcoma, breast cancer, and brain tumors, and they also provide a link between
      the central role of p53 inactivation in human cancer and the well-defined G2
      checkpoint in yeast.
FAU - Bell, D W
AU  - Bell DW
AD  - Massachusetts General Hospital Center for Cancer Risk Analysis and Harvard
      Medical School, Building 149, Charlestown, MA 02129, USA.
FAU - Varley, J M
AU  - Varley JM
FAU - Szydlo, T E
AU  - Szydlo TE
FAU - Kang, D H
AU  - Kang DH
FAU - Wahrer, D C
AU  - Wahrer DC
FAU - Shannon, K E
AU  - Shannon KE
FAU - Lubratovich, M
AU  - Lubratovich M
FAU - Verselis, S J
AU  - Verselis SJ
FAU - Isselbacher, K J
AU  - Isselbacher KJ
FAU - Fraumeni, J F
AU  - Fraumeni JF
FAU - Birch, J M
AU  - Birch JM
FAU - Li, F P
AU  - Li FP
FAU - Garber, J E
AU  - Garber JE
FAU - Haber, D A
AU  - Haber DA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.11 (Checkpoint Kinase 2)
RN  - EC 2.7.11.1 (CHEK2 protein, human)
RN  - EC 2.7.11.1 (Checkpoint Kinase 1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
CIN - Science. 1999 Dec 24;286(5449):2433-4. PMID: 10636795
MH  - Alleles
MH  - Apoptosis
MH  - Brain Neoplasms/genetics
MH  - Breast Neoplasms/genetics
MH  - Checkpoint Kinase 1
MH  - Checkpoint Kinase 2
MH  - Female
MH  - G1 Phase
MH  - *G2 Phase
MH  - *Genes, Tumor Suppressor
MH  - Genes, p53
MH  - Genetic Predisposition to Disease
MH  - *Germ-Line Mutation
MH  - Heterozygote
MH  - Humans
MH  - Li-Fraumeni Syndrome/enzymology/*genetics/pathology
MH  - Male
MH  - Pedigree
MH  - Polymorphism, Genetic
MH  - Protein Kinases/genetics
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - Sarcoma/genetics
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
EDAT- 2000/01/05 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/01/05 09:00
PHST- 2000/01/05 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/01/05 09:00 [entrez]
AID - 8128 [pii]
AID - 10.1126/science.286.5449.2528 [doi]
PST - ppublish
SO  - Science. 1999 Dec 24;286(5449):2528-31. doi: 10.1126/science.286.5449.2528.