The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression

Winfried Edelmann; Asad Umar; Kan Yang; Joerg Heyer; Melanie Kucherlapati; Marie Lia; Burkhard Kneitz; Elena Avdievich; Kunhua Fan; Edmund Wong; Gray Crouse; Thomas Kunkel; Martin Lipkin; Richard D. Kolodner; Raju Kucherlapati

The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression

Winfried Edelmann, Asad Umar, Kan Yang, Joerg Heyer, Melanie Kucherlapati, Marie Lia, Burkhard Kneitz, Elena Avdievich, Kunhua Fan, Edmund Wong, Gray Crouse, Thomas Kunkel, Martin Lipkin, Richard D. Kolodner, Raju Kucherlapati

Cell Biology

Research output: Contribution to journal › Article › peer-review

143 Scopus citations

Abstract

Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.

Original language	English (US)
Pages (from-to)	803-807
Number of pages	5
Journal	Cancer research
Volume	60
Issue number	4
State	Published - Feb 15 2000

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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Cite this

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title = "The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression",

abstract = "Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.",

author = "Winfried Edelmann and Asad Umar and Kan Yang and Joerg Heyer and Melanie Kucherlapati and Marie Lia and Burkhard Kneitz and Elena Avdievich and Kunhua Fan and Edmund Wong and Gray Crouse and Thomas Kunkel and Martin Lipkin and Kolodner, {Richard D.} and Raju Kucherlapati",

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volume = "60",

pages = "803--807",

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AU - Edelmann, Winfried

AU - Umar, Asad

AU - Yang, Kan

AU - Heyer, Joerg

AU - Kucherlapati, Melanie

AU - Lia, Marie

AU - Kneitz, Burkhard

AU - Avdievich, Elena

AU - Fan, Kunhua

AU - Wong, Edmund

AU - Crouse, Gray

AU - Kunkel, Thomas

AU - Lipkin, Martin

AU - Kolodner, Richard D.

AU - Kucherlapati, Raju

PY - 2000/2/15

Y1 - 2000/2/15

N2 - Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.

AB - Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.

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AN - SCOPUS:0034652474

SN - 0008-5472

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JO - Cancer Research

JF - Cancer Research

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ER -

The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression

Abstract

ASJC Scopus subject areas

UN SDGs

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