Potential contributions of antimutator activity to the metastasis suppressor function of NM23-H1.
nm23-h1 is a well-documented metastasis suppressor gene whose mechanism(s) of action have yet to be fully elucidated. The purpose of this report is to discuss recent advances in investigating the potential role of a novel 3'-5' exonuclease activity identified recently in our laboratory, a biochemical function associated, in general, with DNA repair and replication. We have employed a site-directed mutagenesis approach to demonstrate that the 3'-5' exonuclease activity of NM23-H1 is required for its metastasis suppressor function. Consistent with a role in DNA repair, we also observe that the single yeast NM23 homolog (YNK1) is required for the maintenance of genomic integrity and normal kinetics of DNA repair in response to exposure to ultraviolet radiation. These results and their implications for understanding the molecular mechanisms underlying NM23-H1 functions in cancer are discussed.
Kaetzel
David M
DM
Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0298, USA. dmkaetz@uky.edu
McCorkle
Joseph R
JR
Novak
Marian
M
Yang
Mengmeng
M
Jarrett
Stuart G
SG
D045744:Cell Line, Tumor; D004260:DNA Repair; D005092:Exonucleases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000517:prevention & control
D054778:NM23 Nucleoside Diphosphate Kinases; D005092:Exonucleases