Chromodomain-helicase-DNA-binding protein 1-like (ALC1) is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''CHD1L''
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 ...
.
It has been implicated in chromatin remodeling and DNA relaxation process required for DNA replication, repair and transcription. The ALC1 comprises ATPase domain and macro domain. On the basis of homology within the ATPase domain, ALC1 belongs to Snf2 family.
It has 897 amino acids and is approximately 101kDa in size.
Function
In development
CHD1L, a DNA
helicase
Helicases are a class of enzymes that are vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic double helix, separating the two hybridized ...
, possesses
chromatin remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...
activity and interacts with
PARP1/PARylation in regulating pluripotency during
development
Development or developing may refer to:
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al reprogramming. The CHD1L macro-domain interacts with the PAR moiety of PARylated-PARP1 to facilitate early-stage reprogramming and
pluripotency
Cell potency is a cell's ability to differentiate into other cell types.
The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...
in stem cells.
It appears that CHD1L expression is vital for early events in
embryonic development
In developmental biology, animal embryonic development, also known as animal embryogenesis, is the developmental stage of an animal embryo. Embryonic development starts with the fertilization of an egg cell (ovum) by a sperm, sperm cell (spermat ...
.
CHD1L's role in embryonic development is related to its role as a transcriptional activator of several genes (Akt, METP2, TCF4) which lead to EMT (epithelial to mesenchymal transition) Notably, EMT is also implicated in tumor metastasis, further complicating CHD1L's role in both healthy and diseased cells.
In DNA repair
To allow the critical cellular process of DNA repair, the chromatin must be remodeled at sites of damage. CHD1L (ALC1) a
chromatin remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...
protein, acts very early in DNA repair. Chromatin relaxation occurs rapidly at the site of a DNA damage.
This process is initiated by
PARP1 protein that starts to appear at DNA damage in less than a second, with half maximum accumulation within 1.6 seconds after the damage occurs.
PARP1 then PARylates itself, with these PAR chains attracting the macro domain of CHD1L, relieving autoinhibition and allowing the N-terminal domains to interact with chromatin. The linker between the macro and N-terminal domains wraps around the histone, interacting with the acidic nucleosome patch via an R611 anchor. Next the chromatin remodeler CHD1L (ALC1) quickly attaches to the product of PARP1, and completes arrival at the DNA damage within 10 seconds of the damage.
About half of the maximum chromatin relaxation, due to action of CHD1L (ALC1), occurs by 10 seconds.
This then allows recruitment of the DNA repair enzyme
MRE11, to initiate DNA repair, within 13 seconds.
is involved in
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
al repair. CHD1L (ALC1) is also required for repair of
UV-damaged
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
through
nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. Intercalation (biochemistry), intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single ...
.
Related gene problems
*
1q21.1 deletion syndrome
*
1q21.1 duplication syndrome
With
1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of
helicase
Helicases are a class of enzymes that are vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic double helix, separating the two hybridized ...
with the
Werner syndrome
References
External links
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Further reading
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