PMID- 8261516
OWN - NLM
STAT- MEDLINE
DCOM- 19940121
LR  - 20220321
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 75
IP  - 6
DP  - 1993 Dec 17
TI  - Hypermutability and mismatch repair deficiency in RER+ tumor cells.
PG  - 1227-36
AB  - A subset of sporadic colorectal tumors and most tumors developing in hereditary 
      nonpolyposis colorectal cancer patients display frequent alterations in 
      microsatellite sequences. Such tumors have been thought to manifest replication 
      errors (RER+), but the basis for the alterations has remained conjectural. We 
      demonstrate that the mutation rate of (CA)n repeats in RER+ tumor cells is at 
      least 100-fold that in RER- tumor cells and show by in vitro assay that increased 
      mutability of RER+ cells is associated with a profound defect in strand-specific 
      mismatch repair. This deficiency was observed with microsatellite heteroduplexes 
      as well as with heteroduplexes containing single base-base mismatches and 
      affected an early step in the repair pathway. Thus, a true mutator phenotype 
      exists in a subset of tumor cells, the responsible defect is likely to cause 
      transitions and transversions in addition to microsatellite alterations, and a 
      biochemical basis for this phenotype has been identified.
FAU - Parsons, R
AU  - Parsons R
AD  - Department of Biochemistry, Duke University Medical Center, Durham, North 
      Carolina 27710.
FAU - Li, G M
AU  - Li GM
FAU - Longley, M J
AU  - Longley MJ
FAU - Fang, W H
AU  - Fang WH
FAU - Papadopoulos, N
AU  - Papadopoulos N
FAU - Jen, J
AU  - Jen J
FAU - de la Chapelle, A
AU  - de la Chapelle A
FAU - Kinzler, K W
AU  - Kinzler KW
FAU - Vogelstein, B
AU  - Vogelstein B
FAU - Modrich, P
AU  - Modrich P
LA  - eng
GR  - CA09320/CA/NCI NIH HHS/United States
GR  - CA35494/CA/NCI NIH HHS/United States
GR  - GM45190/GM/NIGMS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Nucleic Acid Heteroduplexes)
RN  - 0 (Oligodeoxyribonucleotides)
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA Repair/*genetics
MH  - DNA Replication/*genetics
MH  - DNA, Neoplasm/metabolism
MH  - Genetic Vectors
MH  - HeLa Cells
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Mutagenesis, Insertional
MH  - *Mutation
MH  - Nucleic Acid Heteroduplexes/metabolism
MH  - Oligodeoxyribonucleotides
MH  - Polymerase Chain Reaction
MH  - Repetitive Sequences, Nucleic Acid
MH  - Restriction Mapping
MH  - Tumor Cells, Cultured
EDAT- 1993/12/17 00:00
MHDA- 1993/12/17 00:01
CRDT- 1993/12/17 00:00
PHST- 1993/12/17 00:00 [pubmed]
PHST- 1993/12/17 00:01 [medline]
PHST- 1993/12/17 00:00 [entrez]
AID - 0092-8674(93)90331-J [pii]
AID - 10.1016/0092-8674(93)90331-j [doi]
PST - ppublish
SO  - Cell. 1993 Dec 17;75(6):1227-36. doi: 10.1016/0092-8674(93)90331-j.