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Target Concepts:
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Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The formation of multiprotein complexes is l'ordre du jour in regulatory pathways. In this issue of Oncogene, Reale et al. report the formation of a particularly sophisticated complex of two important regulatory enzymes, DNMT1 (
DNA methyltransferase
-1) and
PARP-1
(poly(ADP-ribose)polymerase-1). The former evolved with a specific sequence motif binding the enzymatic product of the latter. The product, poly(ADP-ribose), bonds the two partners into a heterodimeric complex and, as a consequence, the catalytic function of DNMT1 is silenced. Thus,
PARP-1
becomes a conditional negative regulator of DNMT1. In a larger perspective, Reale et al. highlight the potential role of
PARP-1
as a co-regulator of DNA methylation leading to epigenetic reprogramming of cancer cells.
...
PMID:Poly(ADP-ribose): a co-regulator of DNA methylation? 1563 86
DNA damage signaling is crucial for the maintenance of genome integrity. In higher eukaryotes a NAD+-dependent signal transduction mechanism has evolved to protect cells against the genome destabilizing effects of DNA strand breaks. The mechanism involves 2 nuclear enzymes that sense DNA strand breaks, poly(ADP-ribose) polymerase-1 and -2 (
PARP-1
and PARP-2). When activated by DNA breaks, these PARPs use NAD+ to catalyze their automodification with negatively charged, long and branched ADP-ribose polymers. Through recruitment of specific proteins at the site of damage and regulation of their activities, these polymers may either directly participate in the repair process or coordinate repair through chromatin unfolding, cell cycle progression, and cell survival-cell death pathways. A number of proteins, including histones, DNA topoisomerases,
DNA methyltransferase
-1 as well as DNA damage repair and checkpoint proteins (p23, p21, DNA-PK, NF-kB, XRCC1, and others) can be targeted in this manner; the interaction involves a specific poly(ADP-ribose)-binding sequence motif of 20-26 amino acids in the target domains.
...
PMID:The role of poly(ADP-ribose) in the DNA damage signaling network. 1595 61
Our previous data have shown that in L929 mouse fibroblasts the control of methylation pattern depends in part on poly(ADP-ribosyl)ation and that ADP-ribose polymers (PARs), both present on poly(ADP-ribosyl)ated
PARP-1
and/or protein-free, have an inhibitory effect on Dnmt1 activity. Here we show that transient ectopic overexpression of CCCTC-binding factor (CTCF) induces PAR accumulation,
PARP-1
, and CTCF poly(ADP-ribosyl)ation in the same mouse fibroblasts. The persistence in time of a high PAR level affects the DNA methylation machinery; the
DNA methyltransferase
activity is inhibited with consequences for the methylation state of genome, which becomes diffusely hypomethylated affecting centromeric minor satellite and B1 DNA repeats. In vitro data show that CTCF is able to activate
PARP-1
automodification even in the absence of nicked DNA. Our new finding that CTCF is able per se to activate
PARP-1
automodification in vitro is of great interest as so far a burst of poly(ADP-ribosyl)ated
PARP-1
has generally been found following introduction of DNA strand breaks. CTCF is unable to inhibit DNMT1 activity, whereas poly(ADP-ribosyl)ated
PARP-1
plays this inhibitory role. These data suggest that CTCF is involved in the cross-talk between poly(ADP-ribosyl)ation and DNA methylation and underscore the importance of a rapid reversal of PARP activity, as DNA methylation pattern is responsible for an important epigenetic code.
...
PMID:CCCTC-binding factor activates PARP-1 affecting DNA methylation machinery. 1853 2
Benzene is an established hematotoxic carcinogen which can cause leukemia. DNA damage and disorder of repair capacity are the crucial mechanisms in leukemogenesis of benzene.
DNA methyltransferase
inhibitor, 5-aza-2'-deoxycytidine (5-aza) and histone deacetylase inhibitor, trichostatin A (TSA) are two kinds of key epigenetic modification reagents. The mRNA expression of poly(ADP-ribose) polymerases-1 (
PARP-1
), a pivotal repair gene, has been decreased by benzene. However, the effect of epigenetic modification on benzene-induced low
PARP-1
expression has not been reported. In this study, lymphoblastoid cell line F32 was incubated by benzene and then further treated with 5-aza and TSA, alone or in combination. The reverse transcription-polymerase chain reaction and methylation-specific PCR were performed to examine the mRNA expression and methylation status of
PARP-1
, respectively. Results showed a dramatic decrease of
PARP-1
mRNA expression and a simultaneously obvious increase in the level of
PARP-1
methylation in benzene-treated cells compared to the control. Further, the
PARP-1
mRNA expression was restored and the level of
PARP-1
methylation was also reduced following epigenetic inhibitors, 5-aza and TSA, alone or in combination treatments. Taken together, methylation of
PARP-1
promoter might be involved in the regulation of benzene-induced decrease of
PARP-1
mRNA expression.
...
PMID:Methylation of PARP-1 promoter involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression. 2023 Aug 82
