PMID- 10535931
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 22
DP  - 1999 Oct 26
TI  - hMutSalpha- and hMutLalpha-dependent phosphorylation of p53 in response to DNA
      methylator damage.
PG  - 12384-8
AB  - hMSH2.hMSH6 heterodimer (hMutSalpha) and hMLH1.hPMS2 complex (hMutLalpha) have
      been implicated in the cytotoxic response of mammalian cells to a number of
      DNA-damaging compounds, including methylating agents that produce
      O(6)-methylguanine (O(6)MeG) adducts. This study demonstrates that O(6)MeG
      lesions, in which the damaged base is paired with either T or C, are subject to
      excision repair in a reaction that depends on a functional mismatch repair
      system. Furthermore, treatment of human cells with the S(N)1 DNA methylators
      N-methyl-N-nitrosourea or N-methyl-N'-nitro-N-nitrosoguanidine results in p53
      phosphorylation on serine residues 15 and 392, and these phosphorylation events
      depend on the presence of functional hMutSalpha and hMutLalpha. Coupled with the 
      previous demonstration that O(6)MeG.T and O(6)MeG.C pairs are recognized by
      hMutSalpha, these results implicate action of the mismatch repair system in the
      initial step of a damage-signaling cascade that can lead to cell-cycle checkpoint
      activation or cell death in response to DNA methylator damage.
FAU - Duckett, D R
AU  - Duckett DR
AD  - Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, NC 
      27710, USA.
FAU - Bronstein, S M
AU  - Bronstein SM
FAU - Taya, Y
AU  - Taya Y
FAU - Modrich, P
AU  - Modrich P
LA  - eng
PT  - Journal Article
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 (Bacterial Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (MSH6 protein, S cerevisiae)
RN  - 0 (MutL protein, E coli)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.1.3 (MutL Proteins)
RN  - EC 3.6.1.3 (MutS DNA Mismatch-Binding Protein)
RN  - EC 3.6.1.3 (MutS protein, E coli)
SB  - IM
MH  - *Adenosine Triphosphatases
MH  - Bacterial Proteins/*metabolism
MH  - Base Pair Mismatch
MH  - Base Sequence
MH  - Cell Line
MH  - *DNA Damage
MH  - *DNA Methylation
MH  - DNA Primers
MH  - *DNA-Binding Proteins
MH  - *Escherichia coli Proteins
MH  - Fungal Proteins/genetics
MH  - Humans
MH  - MutL Proteins
MH  - MutS DNA Mismatch-Binding Protein
MH  - Phosphorylation
MH  - *Saccharomyces cerevisiae Proteins
MH  - Tumor Suppressor Protein p53/*metabolism
PMC - PMC22926
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1073/pnas.96.22.12384 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12384-8. doi:
      10.1073/pnas.96.22.12384.