The Growth Arrest and DNA Damage or ''gadd45''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s, including
GADD45A (originally termed gadd45)
GADD45B (originally termed MyD118), and
GADD45G (originally termed CR6), are implicated as stress sensors that modulate the response of
mammal
A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
ian
cells to
genotoxic/
physiological stress, and modulate
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
formation. Gadd45
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s interact with other proteins implicated in stress responses, including
PCNA
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase delta, DNA polymerase δ in eukaryotic cell (biology), cells and is essential for replication. PCNA is a homotrimer and achieves its ...
,
p21,
Cdc2/CyclinB1,
MEKK4, and
p38 kinase.
GADD45 proteins regulate
differentiation at the two cell stage of
embryogenesis
An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...
, a key stage of
zygotic genome activation. GADD45 likely acts by promoting
TET-mediated
DNA demethylation
For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence ...
leading to the induction of
expression of genes necessary for zygote activation.
Overexpression of the ''GADD45'' gene in the ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
''
nervous system
In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...
significantly increases
longevity
Longevity may refer to especially long-lived members of a population, whereas ''life expectancy'' is defined Statistics, statistically as the average number of years remaining at a given age. For example, a population's life expectancy at birth ...
.
[Plyusnina EN, Shaposhnikov MV, Moskalev AA. Increase of Drosophila melanogaster lifespan due to D-GADD45 overexpression in the nervous system. Biogerontology. 2011 Jun;12(3):211-26. doi: 10.1007/s10522-010-9311-6. Epub 2010 Dec 9. PMID 21153055] This longevity increase can be attributed to more efficient recognition and repair of
spontaneous DNA damages generated by physiological processes and environmental factors.
History
*
Gadd45a was discovered and characterized in the laboratory of Dr.
Albert J. Fornace Jr. in 1988.
*
Gadd45b (MyD118) was discovered and characterized in the laboratories of Drs.
Dan A. Liebermann and Barbara Hoffman in 1991.
*
Gadd45g (CR6) was discovered and characterized in the laboratories of Drs. Kenneth Smith, Dan A. Liebermann, and Barbara Hoffman in 1993 and 1999.
See also
*
GADD45A
*
GADD45B
*
GADD45G
References
External links
*
Mammal genes
{{biochem-stub