TY - CHAP
T1 - DNA methyltransferases, DNA damage repair, and cancer
AU - Jin, Bilian
AU - Robertson, Keith D.
N1 - Funding Information:
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.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84869046975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869046975&partnerID=8YFLogxK
U2 - 10.1007/978-1-4419-9967-2_1
DO - 10.1007/978-1-4419-9967-2_1
M3 - Chapter
C2 - 22956494
AN - SCOPUS:84869046975
SN - 9781441999665
T3 - Advances in Experimental Medicine and Biology
SP - 3
EP - 29
BT - Epigenetic Alterations in Oncogenesis
PB - Springer Science and Business Media, LLC
ER -