Polymerase δ and εin colon cancer

Aaron Stevens

Polymerase δ and ε contain both polymerase and exonuclease domains

Polymerase δ and ε are the major replicative polymerases

Pol δ and ε help repair damage

Mutating the exonuclease domain leads to decreased survival rates

Point mutations in Pol δ are found in colon cancer

Mutating the exonuclease domain of Polymerase δ leads to cancer

References Biard Denis S.F. (2011). New Insight on Entangled DNA Repair Pathways: Stable

Silenced Human Cells for Unraveling the DDR Jigsaw, DNA Repair - On the Pathways to Fixing DNA Damage and Errors, Dr. Francesca Storici (Ed.), ISBN: 978-953-307-649-2, InTech, DOI: 10.5772/23681.

Prindle, M. J. and Loeb, L. A. (2012), DNA polymerase delta in dna replication and genome maintenance. Environ. Mol. Mutagen., 53: 666–682. doi: 10.1002/em.21745

Goldsby RE, Hays LE, Chen X, Olmsted EA, Slayton WB, Spangrude GJ, Preston BD. High incidence of epithelial cancers in mice deficient for DNA polymerase δ proofreading. PNAS.2002;99(24):15560–15565. doi: 10.1073/pnas.232340999.

Burgers P. M. (2009) Polymerase dynamics at the eukaryotic DNA replication fork. J. Biol. Chem. 284, 4041–4045

Albertson T. M., Ogawa M., Bugni J. M., Hays L. E., Chen Y., Wang Y.,Treuting P. M., Heddle J. A., Goldsby R. E., Preston B. D. (2009) DNA polymerase ϵ and δ proofreading suppress discrete mutator and cancer phenotypes in mice.Proc. Natl. Acad. Sci. U.S.A. 106, 17101–17104

Helmut Pospiech and Juhani E. Syväoja, “DNA Polymerase ε - More Than a Polymerase,”TheScientificWorldJOURNAL, vol. 3, pp. 87-104, 2003. doi:10.1100/tsw.2003.08

Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487: 330–337

Q. Zhou, R. Effati, K. Talvinen, H. Pospiech, J.E. Syväoja, Y. Collan. Genomic changes of the 55 kDa subunit of DNA polymerase epsilon in human breast cancer. Cancer Genomics Proteomics, 5 (2008), pp. 287–292