CHD1L

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.{{cite journal | vauthors = Jiang BH, Chen WY, Li HY, Chien Y, Chang WC, Hsieh PC, Wu P, Chen CY, Song HY, Chien CS, Sung YJ, Chiou SH | title = CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming | journal = Stem Cells | volume = 33 | issue = 10 | pages = 2961–72 | date = October 2015 | pmid = 26201266 | pmc = 4832376 | doi = 10.1002/stem.2116 }} It appears that CHD1L expression is vital for early events in embryonic development. {{cite journal | vauthors = Snider AC, Leong D, Wang QT, Wysocka J, Yao MW, Scott MP | title = The chromatin remodeling factor Chd1l is required in the preimplantation embryo | journal = Biology Open | volume = 2 | issue = 2 | pages = 121–31 | date = February 2013 | pmid = 23429299 | pmc = 3575647 | doi = 10.1242/bio.20122949 }} 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){{cite journal | pmc=7934534 | date=2021 | last1=Xiong | first1=X. | last2=Lai | first2=X. | last3=Li | first3=A. | last4=Liu | first4=Z. | last5=Ma | first5=N. | title=Diversity roles of CHD1L in normal cell function and tumorigenesis | journal=Biomarker Research | volume=9 | issue=1 | page=16 | doi=10.1186/s40364-021-00269-w | doi-access=free | pmid=33663617 }} Notably, EMT is also implicated in tumor metastasis,{{cite journal | pmc=4385028 | date=2015 | last1=Heerboth | first1=S. | last2=Housman | first2=G. | last3=Leary | first3=M. | last4=Longacre | first4=M. | last5=Byler | first5=S. | last6=Lapinska | first6=K. | last7=Willbanks | first7=A. | last8=Sarkar | first8=S. | title=EMT and tumor metastasis | journal=Clinical and Translational Medicine | volume=4 | page=6 | doi=10.1186/s40169-015-0048-3 | doi-access=free | pmid=25852822 }} further complicating CHD1L's role in both healthy and diseased cells.

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.{{cite journal | vauthors = Sellou H, Lebeaupin T, Chapuis C, Smith R, Hegele A, Singh HR, Kozlowski M, Bultmann S, Ladurner AG, Timinszky G, Huet S | title = The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage | journal = Molecular Biology of the Cell | volume = 27 | issue = 24 | pages = 3791–3799 | date = December 2016 | pmid = 27733626 | pmc = 5170603 | doi = 10.1091/mbc.E16-05-0269 }} 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.{{cite journal | vauthors = Haince JF, McDonald D, Rodrigue A, Déry U, Masson JY, Hendzel MJ, Poirier GG | title = PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites | journal = The Journal of Biological Chemistry | volume = 283 | issue = 2 | pages = 1197–208 | date = January 2008 | pmid = 18025084 | doi = 10.1074/jbc.M706734200 | doi-access = free }} 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.{{cite journal | pmc=8249414 | date=2021 | last1=Wang | first1=L. | last2=Chen | first2=K. | last3=Chen | first3=Z. | title=Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome | journal=Nature Communications | volume=12 | issue=1 | page=4057 | doi=10.1038/s41467-021-24320-4 | pmid=34210977 }} The linker between the macro and N-terminal domains wraps around the histone, interacting with the acidic nucleosome patch via an R611 anchor.{{cite journal | pmid=33357431 | date=2020 | last1=Lehmann | first1=L. C. | last2=Bacic | first2=L. | last3=Hewitt | first3=G. | last4=Brackmann | first4=K. | last5=Sabantsev | first5=A. | last6=Gaullier | first6=G. | last7=Pytharopoulou | first7=S. | last8=Degliesposti | first8=G. | last9=Okkenhaug | first9=H. | last10=Tan | first10=S. | last11=Costa | first11=A. | last12=Skehel | first12=J. M. | last13=Boulton | first13=S. J. | last14=Deindl | first14=S. | title=Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch | journal=Cell Reports | volume=33 | issue=12 | doi=10.1016/j.celrep.2020.108529 | pmc=7116876 }} 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.{{cite journal | vauthors = 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 | title = PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1 | journal = The Journal of Cell Biology | volume = 199 | issue = 2 | pages = 235–49 | date = October 2012 | pmid = 23045548 | pmc = 3471223 | doi = 10.1083/jcb.201112132 }}

• 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{{cite journal | doi = 10.1186/1750-1172-6-54 | volume=6 | title=Understanding the impact of 1q21.1 copy number variant | year=2011 | journal=Orphanet Journal of Rare Diseases | page=54 | vauthors=Harvard C | pmid=21824431 | pmc=3180300 | doi-access=free }}

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• {{UCSC gene info|CHD1L}}

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• {{cite journal | vauthors = Matoba R, Okubo K, Hori N, Fukushima A, Matsubara K | title = The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression | journal = Gene | volume = 146 | issue = 2 | pages = 199–207 | date = September 1994 | pmid = 8076819 | doi = 10.1016/0378-1119(94)90293-3 }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = 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 | title = Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells | journal = Genome Research | volume = 10 | issue = 10 | pages = 1546–60 | date = October 2000 | pmid = 11042152 | pmc = 310934 | doi = 10.1101/gr.140200 }}
• {{cite journal | vauthors = 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 | title = Creation of genome-wide protein expression libraries using random activation of gene expression | journal = Nature Biotechnology | volume = 19 | issue = 5 | pages = 440–5 | date = May 2001 | pmid = 11329013 | doi = 10.1038/88107 | s2cid = 25064683 }}
• {{cite journal | vauthors = Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG | title = The macro domain is an ADP-ribose binding module | journal = The EMBO Journal | volume = 24 | issue = 11 | pages = 1911–20 | date = June 2005 | pmid = 15902274 | pmc = 1142602 | doi = 10.1038/sj.emboj.7600664 }}
• {{cite journal | vauthors = 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 | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = January 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}

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