CHD1L

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

CHD1L
Identifiers
AliasesCHD1L, ALC1, CHDL, chromodomain helicase DNA binding protein 1-like, chromodomain helicase DNA binding protein 1 like
External IDsOMIM: 613039 MGI: 1915308 HomoloGene: 11590 GeneCards: CHD1L
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1q21.1Start147,242,654 bp[1]
End147,295,765 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

9557

68058

Ensembl

ENSG00000131778

ENSMUSG00000028089

UniProt

Q86WJ1

Q9CXF7

RefSeq (mRNA)

NM_026539

RefSeq (protein)

NP_080815

Location (UCSC)Chr 1: 147.24 – 147.3 MbChr 3: 97.56 – 97.61 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[8] It appears that CHD1L expression is vital for early events in embryonic development. [9]

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.[10] 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.[11] 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.[10] About half of the maximum chromatin relaxation, due to action of CHD1L (ALC1), occurs by 10 seconds.[10] This then allows recruitment of the DNA repair enzyme MRE11, to initiate DNA repair, within 13 seconds.[11] MRE11 is involved in homologous recombinational repair. CHD1L (ALC1) is also required for repair of UV-damaged chromatin through nucleotide excision repair.[12]

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[13]

References

  1. GRCh38: Ensembl release 89: ENSG00000131778 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000028089 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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 (July 1998). "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. Bibcode:1998PNAS...95.8175M. doi:10.1073/pnas.95.14.8175. PMC 20949. PMID 9653160.
  6. "Entrez Gene: CHD1L chromodomain helicase DNA binding protein 1-like".
  7. Flaus A, Martin DM, Barton GJ, Owen-Hughes T (2006-05-31). "Identification of multiple distinct Snf2 subfamilies with conserved structural motifs". Nucleic Acids Research. 34 (10): 2887–905. doi:10.1093/nar/gkl295. PMC 1474054. PMID 16738128.
  8. Jiang BH, Chen WY, Li HY, Chien Y, Chang WC, Hsieh PC, Wu P, Chen CY, Song HY, Chien CS, Sung YJ, Chiou SH (October 2015). "CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming". Stem Cells. 33 (10): 2961–72. doi:10.1002/stem.2116. PMC 4832376. PMID 26201266.
  9. Snider AC, Leong D, Wang QT, Wysocka J, Yao MW, Scott MP (February 2013). "The chromatin remodeling factor Chd1l is required in the preimplantation embryo". Biology Open. 2 (2): 121–31. doi:10.1242/bio.20122949. PMC 3575647. PMID 23429299.
  10. Sellou H, Lebeaupin T, Chapuis C, Smith R, Hegele A, Singh HR, Kozlowski M, Bultmann S, Ladurner AG, Timinszky G, Huet S (December 2016). "The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage". Molecular Biology of the Cell. 27 (24): 3791–3799. doi:10.1091/mbc.E16-05-0269. PMC 5170603. PMID 27733626.
  11. Haince JF, McDonald D, Rodrigue A, Déry U, Masson JY, Hendzel MJ, Poirier GG (January 2008). "PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites". The Journal of Biological Chemistry. 283 (2): 1197–208. doi:10.1074/jbc.M706734200. PMID 18025084.
  12. 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 (October 2012). "PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1". The Journal of Cell Biology. 199 (2): 235–49. doi:10.1083/jcb.201112132. PMC 3471223. PMID 23045548.
  13. Harvard C (2011). "Understanding the impact of 1q21.1 copy number variant". Orphanet Journal of Rare Diseases. 6: 54. doi:10.1186/1750-1172-6-54. PMC 3180300. PMID 21824431.

Further reading


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