PMID- 10078208
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20180227
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 3
IP  - 2
DP  - 1999 Feb
TI  - hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA.
PG  - 255-61
AB  - Mismatch recognition by the human MutS homologs hMSH2-hMSH6 is regulated by
      adenosine nucleotide binding, supporting the hypothesis that it functions as a
      molecular switch. Here we show that ATP-induced release of hMSH2-hMSH6 from
      mismatched DNA is prevented if the ends are blocked or if the DNA is circular. We
      demonstrate that mismmatched DNA provokes ADP-->ATP exchange, resulting in a
      discernible conformational transition that converts hMSH2-hMSH6 into a sliding
      clamp capable of hydrolysis-independent diffusion along the DNA backbone. Our
      results support a model for bidirectional mismatch repair in which stochastic
      loading of multiple ATP-bound hMSH2-hMSH6 sliding clamps onto mismatch-containing
      DNA leads to activation of the repair machinery and/or other signaling effectors 
      similar to G protein switches.
FAU - Gradia, S
AU  - Gradia S
AD  - Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson
      University, Philadelphia, Pennsylvania 19107, USA.
FAU - Subramanian, D
AU  - Subramanian D
FAU - Wilson, T
AU  - Wilson T
FAU - Acharya, S
AU  - Acharya S
FAU - Makhov, A
AU  - Makhov A
FAU - Griffith, J
AU  - Griffith J
FAU - Fishel, R
AU  - Fishel R
LA  - eng
GR  - R01 CA067007/CA/NCI NIH HHS/United States
GR  - CA56542/CA/NCI NIH HHS/United States
GR  - CA67007/CA/NCI NIH HHS/United States
GR  - GM31819/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (Bacterial Proteins)
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 (Proto-Oncogene Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.1.3 (MSH2 protein, human)
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 Homolog 2 Protein)
RN  - EC 3.6.1.3 (MutS protein, E coli)
RN  - I38ZP9992A (Magnesium)
SB  - IM
MH  - *Adenosine Triphosphatases
MH  - Adenosine Triphosphate/physiology
MH  - Bacterial Proteins/physiology
MH  - Base Pairing
MH  - *DNA Damage
MH  - *DNA Repair
MH  - *DNA-Binding Proteins
MH  - Diffusion
MH  - *Escherichia coli Proteins
MH  - Fungal Proteins/*physiology
MH  - Humans
MH  - Hydrolysis
MH  - Magnesium/physiology
MH  - Models, Genetic
MH  - MutL Proteins
MH  - MutS DNA Mismatch-Binding Protein
MH  - MutS Homolog 2 Protein
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins/*physiology
MH  - *Saccharomyces cerevisiae Proteins
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
AID - S1097-2765(00)80316-0 [pii]
PST - ppublish
SO  - Mol Cell. 1999 Feb;3(2):255-61.