DNA methyltransferases, DNA damage repair, and cancer

Bilian Jin, Keith D Robertson

Research output: Contribution to journalArticle

193 Citations (Scopus)

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)
Pages (from-to)3-29
Number of pages27
JournalAdvances in Experimental Medicine and Biology
Volume754
DOIs
StatePublished - 2013
Externally publishedYes

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Methyltransferases
DNA Methylation
DNA Repair
DNA Damage
Repair
DNA
Genes
Neoplasms
Tumors
Genomic Instability
Tumor Suppressor Genes
Carcinogenesis
Chromosomes
Maintenance
Mountings
Genome
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

DNA methyltransferases, DNA damage repair, and cancer. / Jin, Bilian; Robertson, Keith D.

In: Advances in Experimental Medicine and Biology, Vol. 754, 2013, p. 3-29.

Research output: Contribution to journalArticle

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