CHD1L explained

Chromodomain-helicase-DNA-binding protein 1-like (ALC1) is an enzyme that in humans is encoded by the CHD1L gene.^{[1] [2]} 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.^[3]

It has 897 amino acids and is approximately 101kDa in size.^[4]

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.^[5] It appears that CHD1L expression is vital for early events in embryonic development. ^[6]

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.^[7] 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.^[8] 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. MRE11 is involved in homologous recombinational repair. CHD1L (ALC1) is also required for repair of UV-damaged chromatin through nucleotide excision repair.^[9]

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 with the Werner syndrome^[10]

Further reading

• Matoba R, Okubo K, Hori N, Fukushima A, Matsubara K . The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression . Gene . 146 . 2 . 199–207 . September 1994 . 8076819 . 10.1016/0378-1119(94)90293-3 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–60 . October 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
• Harrington JJ, Sherf B, Rundlett S, Jackson PD, Perry R, Cain S, Leventhal C, Thornton M, Ramachandran R, Whittington J, Lerner L, Costanzo D, McElligott K, Boozer S, Mays R, Smith E, Veloso N, Klika A, Hess J, Cothren K, Lo K, Offenbacher J, Danzig J, Ducar M . Creation of genome-wide protein expression libraries using random activation of gene expression . Nature Biotechnology . 19 . 5 . 440–5 . May 2001 . 11329013 . 10.1038/88107 . 25064683 .
• Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG . The macro domain is an ADP-ribose binding module . The EMBO Journal . 24 . 11 . 1911–20 . June 2005 . 15902274 . 1142602 . 10.1038/sj.emboj.7600664 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .

Notes and References

1. Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, Shen Y, Gu J, Yu YP, Xu SH, Wang YX, Chen SJ, Chen Z . Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning . Proceedings of the National Academy of Sciences of the United States of America . 95 . 14 . 8175–80 . July 1998 . 9653160 . 20949 . 10.1073/pnas.95.14.8175 . 1998PNAS...95.8175M . free .
2. Web site: Entrez Gene: CHD1L chromodomain helicase DNA binding protein 1-like.
3. Flaus A, Martin DM, Barton GJ, Owen-Hughes T . Identification of multiple distinct Snf2 subfamilies with conserved structural motifs . Nucleic Acids Research . 34 . 10 . 2887–905 . 2006-05-31 . 16738128 . 1474054 . 10.1093/nar/gkl295 .
4. Web site: UniProt . UniProt .
5. Jiang BH, Chen WY, Li HY, Chien Y, Chang WC, Hsieh PC, Wu P, Chen CY, Song HY, Chien CS, Sung YJ, Chiou SH . CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming . Stem Cells . 33 . 10 . 2961–72 . October 2015 . 26201266 . 4832376 . 10.1002/stem.2116 .
6. Snider AC, Leong D, Wang QT, Wysocka J, Yao MW, Scott MP . The chromatin remodeling factor Chd1l is required in the preimplantation embryo . Biology Open . 2 . 2 . 121–31 . February 2013 . 23429299 . 3575647 . 10.1242/bio.20122949 .
7. Sellou H, Lebeaupin T, Chapuis C, Smith R, Hegele A, Singh HR, Kozlowski M, Bultmann S, Ladurner AG, Timinszky G, Huet S . The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage . Molecular Biology of the Cell . 27 . 24 . 3791–3799 . December 2016 . 27733626 . 5170603 . 10.1091/mbc.E16-05-0269 .
8. Haince JF, McDonald D, Rodrigue A, Déry U, Masson JY, Hendzel MJ, Poirier GG . PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites . The Journal of Biological Chemistry . 283 . 2 . 1197–208 . January 2008 . 18025084 . 10.1074/jbc.M706734200 . free .
9. Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, Hensbergen P, Deelder A, de Groot A, Matsumoto S, Sugasawa K, Thoma N, Vermeulen W, Vrieling H, Mullenders L . PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1 . The Journal of Cell Biology . 199 . 2 . 235–49 . October 2012 . 23045548 . 3471223 . 10.1083/jcb.201112132 .
10. 10.1186/1750-1172-6-54 . 6 . Understanding the impact of 1q21.1 copy number variant . 2011 . Orphanet Journal of Rare Diseases . 54 . Harvard C . 21824431 . 3180300 . free .