Mutated genes in cancer (14) – WRN

WRN

In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 7486 or WRN

● Ensembl (http://www.ensembl.org/index.html): ENSG00000165392

● UniProt (http://www.uniprot.org/): Q14191

● OMIM (http://www.ncbi.nlm.nih.gov/omim):  604611

● GeneCards (http://www.genecards.org/): WRN

● HGNC (http://www.genenames.org/): 12791 or WRN

● Enzyme Number (IUBMB): EC 3.1.-.-, EC 3.6.1.-, EC 3.6.4.12

Gene locus:

8p12

Protein name:

Werner syndrome, RecQ helicase-like

Protein Size:

1432 amino acids; about 162 kDa

Function:

This gene encodes a member of the RecQ subfamily and the DEAH (Asp-Glu-Ala-His) subfamily of DNA and RNA helicases. DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination, and repair. The protein possesses an intrinsic 3' to 5' DNA helicase activity, and is also a 3' to 5' exonuclease.

Werner syndrome, RecQ helicase-like functionally interacts with DNA polymerase delta (POLD1) and replication protein A (RPA) complex, which are required for DNA replication and DNA repair, with Ku70/80 heterodimer which is involved in double strand DNA break repair by non-homologous DNA end joining, and with p53.

Cancer-related alterations:

WRN mutations are a cause of Werner syndrome (WRN). WRN is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction. To date, all known WRN mutations produces prematurely terminated proteins.

Germinal WRN mutations are located over the entire gene and include stop codons, insertions/deletions and exon deletions: not a single missense mutation has been identified so far.

Somatic mutations in WRN have been associated with colon cancer. These mutations are substitutions.

References (open access):

The Werner syndrome protein: linking the replication checkpoint response to genome stability. Pichierri P, Ammazzalorso F, Bignami M, Franchitto A. Aging (Albany NY). 2011 Mar;3(3):311-8.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091524/pdf/aging-03-311.pdf

Roles of Werner syndrome protein in protection of genome integrity. Rossi ML, Ghosh AK, Bohr VA. DNA Repair (Amst). 2010 Mar 2;9(3):331-44.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827637/pdf/nihms168476.pdf