Defective NTHL1 substrate processing

Stable Identifier
R-HSA-9630221
Type
Pathway
Species
Homo sapiens
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NTHL1 D239Y is produced as a consequence of a single nucleotide polymorphism (SNP) rs3087468 in the NTHL1 gene. The frequency of this polymorphism varies in different populations. Substitution of aspartic acid residue at position 239 with tyrosine results in an NTHL1 protein that is still able to bind to damaged DNA but appears to have impaired glycosylase activity. Expression of NTHL1 D239Y in non-transformed human and mouse mammary epithelial cells increases genomic instability and leads to neoplastic transformation, acting as a dominant negative for wild-type NTHL1, through competition for substrate binding (Galick et al. 2013). It is uncertain if heterozygosity for NTHL1 D239Y polymorphism increases predisposition to cancer.

Literature References
PubMed ID Title Journal Year
23940330 Germ-line variant of human NTH1 DNA glycosylase induces genomic instability and cellular transformation

Galick, HA, Kathe, S, Liu, M, Robey-Bond, S, Kidane, D, Wallace, SS, Sweasy, JB

Proc. Natl. Acad. Sci. U.S.A. 2013
Participants
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Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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