Chromodomain-helicase-DNA-binding protein 1-like (ALC1) is an enzyme that in humans is encoded by the CHD1Lgene.[5][6] 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.[7]
It has 897 amino acids and is approximately 101kDa in size.[8]
Function
In development
CHD1L, a DNA helicase, possesses chromatin remodeling activity and interacts with PARP1/PARylation in regulating pluripotency during developmental reprogramming. The CHD1L macro-domain interacts with the PAR moiety of PARylated-PARP1 to facilitate early-stage reprogramming and pluripotency in stem cells.[9] It appears that CHD1L expression is vital for early events in embryonic development. [10] 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)[11] Notably, EMT is also implicated in tumor metastasis,[12] 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 protein, acts very early in DNA repair. Chromatin relaxation occurs rapidly at the site of a DNA damage.[13] 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.[14] 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.[15] The linker between the macro and N-terminal domains wraps around the histone, interacting with the acidic nucleosome patch via an R611 anchor.[16] 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.[13] About half of the maximum chromatin relaxation, due to action of CHD1L (ALC1), occurs by 10 seconds.[13] This then allows recruitment of the DNA repair enzyme MRE11, to initiate DNA repair, within 13 seconds.[14]MRE11 is involved in homologous recombinational repair. CHD1L (ALC1) is also required for repair of UV-damaged chromatin through nucleotide excision repair.[17]
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