Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer

Steven H. Wooden; Heather M. Bassett; Thomas G. Wood; Amanda K. McCullough

doi:10.1016/j.canlet.2003.10.006

Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer

Steven H. Wooden, Heather M. Bassett, Thomas G. Wood, Amanda K. McCullough

Biochemistry & Molecular Biology

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

37 Scopus citations

Abstract

Mutations found in human tumors often include transversions of GC to TA that may result from the mis-pairing of 8-oxoG with adenine during DNA replication. The human MutY (hMYH) enzyme, an adenine-specific DNA glycosylase, initiates repair at this mismatch. It has recently been demonstrated that inherited variants of hMYH may predispose individuals to multiple colorectal adenomas and carcinoma [Nat. Genet. 30 (2002) 227]. In this study, we demonstrate that two of these cancer-associated hMYH mutants, Y165C and G382D, are devoid of glycosylase activity directed towards 8-oxoG:A mispairs. These findings implicate a total loss of hMYH function associated with colorectal cancers.

Original language	English (US)
Pages (from-to)	89-95
Number of pages	7
Journal	Cancer Letters
Volume	205
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2003.10.006
State	Published - Mar 8 2004

Keywords

Cancer
Colorectal adenomas
DNA repair
MutY
Oxidative damage

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/j.canlet.2003.10.006

Cite this

@article{7f17e41487d0413ca8e1edff804a9284,

title = "Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer",

abstract = "Mutations found in human tumors often include transversions of GC to TA that may result from the mis-pairing of 8-oxoG with adenine during DNA replication. The human MutY (hMYH) enzyme, an adenine-specific DNA glycosylase, initiates repair at this mismatch. It has recently been demonstrated that inherited variants of hMYH may predispose individuals to multiple colorectal adenomas and carcinoma [Nat. Genet. 30 (2002) 227]. In this study, we demonstrate that two of these cancer-associated hMYH mutants, Y165C and G382D, are devoid of glycosylase activity directed towards 8-oxoG:A mispairs. These findings implicate a total loss of hMYH function associated with colorectal cancers.",

keywords = "Cancer, Colorectal adenomas, DNA repair, MutY, Oxidative damage",

author = "Wooden, {Steven H.} and Bassett, {Heather M.} and Wood, {Thomas G.} and McCullough, {Amanda K.}",

note = "Funding Information: This work was supported by AG17432 and Center grant ES06676. ",

year = "2004",

month = mar,

day = "8",

doi = "10.1016/j.canlet.2003.10.006",

language = "English (US)",

volume = "205",

pages = "89--95",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer

AU - Wooden, Steven H.

AU - Bassett, Heather M.

AU - Wood, Thomas G.

AU - McCullough, Amanda K.

N1 - Funding Information: This work was supported by AG17432 and Center grant ES06676.

PY - 2004/3/8

Y1 - 2004/3/8

N2 - Mutations found in human tumors often include transversions of GC to TA that may result from the mis-pairing of 8-oxoG with adenine during DNA replication. The human MutY (hMYH) enzyme, an adenine-specific DNA glycosylase, initiates repair at this mismatch. It has recently been demonstrated that inherited variants of hMYH may predispose individuals to multiple colorectal adenomas and carcinoma [Nat. Genet. 30 (2002) 227]. In this study, we demonstrate that two of these cancer-associated hMYH mutants, Y165C and G382D, are devoid of glycosylase activity directed towards 8-oxoG:A mispairs. These findings implicate a total loss of hMYH function associated with colorectal cancers.

AB - Mutations found in human tumors often include transversions of GC to TA that may result from the mis-pairing of 8-oxoG with adenine during DNA replication. The human MutY (hMYH) enzyme, an adenine-specific DNA glycosylase, initiates repair at this mismatch. It has recently been demonstrated that inherited variants of hMYH may predispose individuals to multiple colorectal adenomas and carcinoma [Nat. Genet. 30 (2002) 227]. In this study, we demonstrate that two of these cancer-associated hMYH mutants, Y165C and G382D, are devoid of glycosylase activity directed towards 8-oxoG:A mispairs. These findings implicate a total loss of hMYH function associated with colorectal cancers.

KW - Cancer

KW - Colorectal adenomas

KW - DNA repair

KW - MutY

KW - Oxidative damage

UR - http://www.scopus.com/inward/record.url?scp=1242338775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1242338775&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2003.10.006

DO - 10.1016/j.canlet.2003.10.006

M3 - Article

C2 - 15036665

AN - SCOPUS:1242338775

SN - 0304-3835

VL - 205

SP - 89

EP - 95

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -

Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this