DNA methyltransferases, DNA damage repair, and cancer

Bilian Jin, Keith D. Robertson

Research output: Chapter in Book/Report/Conference proceedingChapter

215 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationEpigenetic Alterations in Oncogenesis
EditorsAdam Karpf
Pages3-29
Number of pages27
DOIs
StatePublished - Jan 1 2013

Publication series

NameAdvances in Experimental Medicine and Biology
Volume754
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'DNA methyltransferases, DNA damage repair, and cancer'. Together they form a unique fingerprint.

  • Cite this

    Jin, B., & Robertson, K. D. (2013). DNA methyltransferases, DNA damage repair, and cancer. In A. Karpf (Ed.), Epigenetic Alterations in Oncogenesis (pp. 3-29). (Advances in Experimental Medicine and Biology; Vol. 754). https://doi.org/10.1007/978-1-4419-9967-2-1