PMID- 10500142
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 20
DP  - 1999 Sep 28
TI  - Purification and DNA binding properties of the ataxia-telangiectasia gene product
      ATM.
PG  - 11134-9
AB  - The human neurodegenerative and cancer predisposition condition
      ataxia-telangiectasia is characterized at the cellular level by radiosensitivity,
      chromosomal instability, and impaired induction of ionizing radiation-induced
      cell cycle checkpoint controls. Recent work has revealed that the gene defective 
      in ataxia-telangiectasia, termed ATM, encodes an approximately 350-kDa
      polypeptide, ATM, that is a member of the phosphatidylinositol 3-kinase family.
      We show that ATM binds DNA and exploit this to purify ATM to near homogeneity.
      Atomic force microscopy reveals that ATM exists in two populations, with sizes
      consistent with monomeric and tetrameric states. Atomic force microscopy analyses
      also show that ATM binds preferentially to DNA ends. This property is similar to 
      that displayed by the DNA-dependent protein kinase catalytic subunit, a
      phosphatidylinositol 3-kinase family member that functions in DNA damage
      detection in conjunction with the DNA end-binding protein Ku. Furthermore,
      purified ATM contains a kinase activity that phosphorylates serine-15 of p53 in a
      DNA-stimulated manner. These results provide a biochemical assay system for ATM, 
      support genetic data indicating distinct roles for DNA-dependent protein kinase
      and ATM, and suggest how ATM may signal the presence of DNA damage to p53 and
      other downstream effectors.
FAU - Smith, G C
AU  - Smith GC
AD  - Wellcome Trust, Institute of Cancer, Department of Zoology, Tennis Court Road,
      Cambridge CB2 1QR, United Kingdom.
FAU - Cary, R B
AU  - Cary RB
FAU - Lakin, N D
AU  - Lakin ND
FAU - Hann, B C
AU  - Hann BC
FAU - Teo, S H
AU  - Teo SH
FAU - Chen, D J
AU  - Chen DJ
FAU - Jackson, S P
AU  - Jackson SP
LA  - eng
GR  - R01 CA050519/CA/NCI NIH HHS/United States
GR  - R37 CA050519/CA/NCI NIH HHS/United States
GR  - CA50519/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Ataxia Telangiectasia/*genetics
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Cell Cycle Proteins
MH  - DNA/*metabolism
MH  - DNA Damage
MH  - DNA-Binding Proteins
MH  - HeLa Cells
MH  - Humans
MH  - Microscopy, Atomic Force
MH  - Phosphorylation
MH  - *Protein-Serine-Threonine Kinases
MH  - Proteins/*isolation & purification/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Tumor Suppressor Proteins
PMC - PMC17999
EDAT- 1999/09/29 00:00
MHDA- 1999/09/29 00:01
CRDT- 1999/09/29 00:00
PHST- 1999/09/29 00:00 [pubmed]
PHST- 1999/09/29 00:01 [medline]
PHST- 1999/09/29 00:00 [entrez]
AID - 10.1073/pnas.96.20.11134 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11134-9. doi:
      10.1073/pnas.96.20.11134.