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DNA Methyltransferases, DNA Damage Repair, and Cancer

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Epigenetic Alterations in Oncogenesis

Part of the book series: Advances in Experimental Medicine and Biology ((volume 754))

Abstract

The maintenance DNA methyltransferase (DNMT) 1 and the de novo methyltransferases DNMT3A and DNMT3B are all essential for mammalian development. DNA methylation, catalyzed by the DNMTs, plays an important role in maintaining genome stability. Aberrant expression of DNMTs and disruption of DNA methylation patterns are closely associated with many forms of cancer, although the exact mechanisms underlying this link remain elusive. DNA damage repair systems have evolved to act as a genome-wide surveillance mechanism to maintain chromosome integrity by recognizing and repairing both exogenous and endogenous DNA insults. Impairment of these systems gives rise to mutations and directly contributes to tumorigenesis. Evidence is mounting for a direct link between DNMTs, DNA methylation, and DNA damage repair systems, which provide new insight into the development of cancer. Like tumor suppressor genes, an array of DNA repair genes frequently sustain promoter hypermethylation in a variety of tumors. In addition, DNMT1, but not the DNMT3s, appear to function coordinately with DNA damage repair pathways to protect cells from sustaining mutagenic events, which is very likely through a DNA methylation-independent mechanism. This chapter is focused on reviewing the links between DNA methylation and the DNA damage response.

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Acknowledgments

Work in the Robertson laboratory is supported by NIH grants R01CA116028, R01CA114229, and the Georgia Cancer Coalition (KDR). KDR is a Georgia Cancer Coalition Distinguished Cancer Scholar.

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  1. Department of Biochemistry and Molecular Biology, Georgia Health Sciences University Cancer Center, CN-2151, 1410 Laney Walker Blvd, Augusta, GA, 30912, USA

    Bilian Jin & Keith D. Robertson

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  1. Bilian Jin
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Correspondence to Keith D. Robertson .

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  1. University of Nebraska Medical Center, Eppley Institute for Research in Cancer, 985950 Nebraska Medical Center, Omaha, 68198, Nebraska, USA

    Adam R. Karpf

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Jin, B., Robertson, K.D. (2013). DNA Methyltransferases, DNA Damage Repair, and Cancer. In: Karpf, A. (eds) Epigenetic Alterations in Oncogenesis. Advances in Experimental Medicine and Biology, vol 754. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9967-2_1

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