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Chromatin assembly factor 1

October 28, 2023

Chromatin assembly factor-1 (CAF-1) is a protein complex — including Chaf1a (p150),  Chaf1b (p60), and p48 subunits in humans, or Cac1, Cac2, and Cac3, respectively, in yeast— that assembles histone tetramers onto replicating DNA during the S phase of the cell cycle.[1][2][3][4]

Steps in nucleosome assembly. CAF-1 is shown in yellow interacting with the H3-H4 tetramer.

Function edit

CAF-1 functions as a histone chaperone that mediates the first step in nucleosome formation by tetramerizing and depositing newly synthesized histone H3/H4 onto DNA rapidly behind replication forks.[5][6][7] H3 and H4 are synthesized in the cytoplasm.[4] Several studies have shown that the interaction between CAF-1 and PCNA (proliferating cell nuclear antigen, which stabilizes CAF-1 at replication forks, is important for CAF-1's role in nucleosome assembly[8]

The three subunits work together to make the complex function. The human subunit (p150) interacts with PCNA, which acts as a sliding clamp, to help the CAF-1 complex interact with the DNA replication fork. Additionally, p150 along with PCNA performs nucleotide excision repair to fix any damaged DNA. P60 interacts with ASF1a/b, which is a histone chaperone for H3/H4. p48 has roles outside of CAF-1, but when involved with the complex, it binds to H4.[4]

p60 attracts ASF1a/b which is a chaperone for H3/H4 and this is in the complex with p150 which interacts with PCNA to attach to the replication fork. The CAF-1 complex adds the histones to the DNA ahead of the replication fork.[4]

A mutation in p150 that results in a loss of function would lead to double stranded breaks, interruptions in the replication fork and translocations. In p60, loss of function would mean the histone chaperone for H3/H4 would not interact with the complex. A mutation like this in either subunit would result in loss of function for the CAF-1 complex as a whole. However, loss of function in p48 would alter how well the complex is able to chaperone chromatin, but would not stop it as a whole.[4]

Roles edit

CAF-1 is required for the spatial organization and epigenetic marking of heterochromatin domains in pluripotent embryonic cells, creating a cellular memory of somatic cell identity during cellular differentiation.[9]

Cells resembling 2-cell-stage mouse embryos (totipotent cells) can be induced in vitro through downregulation of the chromatin-assembly activity of CAF-1 in embryonic stem cells.[10]

CAF-1 forms a deadenylase complex with CCR4-Not, which should not be confused with the unrelated CCR4. The CAF-1/CCR4-Not complex cooperates with the release factor eRF3 and PABPC1 to shorten the poly(A) tail of mRNA during translation.[11]

References edit

  1. ^ Fang, Dong; Han, Junhong (2020-11-06). Histone Mutations and Cancer. Springer Nature. ISBN 978-981-15-8104-5.
  2. ^ Smith S, Stillman B (July 1989). "Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro". Cell. 58 (1): 15–25. doi:10.1016/0092-8674(89)90398-X. PMID 2546672. S2CID 10515064.
  3. ^ Hoek M, Stillman B (October 2003). "Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in vivo". Proceedings of the National Academy of Sciences of the United States of America. 100 (21): 12183–12188. Bibcode:2003PNAS..10012183H. doi:10.1073/pnas.1635158100. PMC 218733. PMID 14519857.
  4. ^ a b c d e Volk, Andrew; Crispino, John D. (August 2015). "The role of the chromatin assembly complex (CAF-1) and its p60 subunit (CHAF1b) in homeostasis and disease". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1849 (8): 979–986. doi:10.1016/j.bbagrm.2015.05.009. ISSN 0006-3002. PMC 4515380. PMID 26066981.
  5. ^ Liu WH, Roemer SC, Zhou Y, Shen ZJ, Dennehey BK, Balsbaugh JL, et al. (September 2016). "The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones". eLife. 5: e18023. doi:10.7554/eLife.18023. PMC 5045291. PMID 27690308.
  6. ^ Sauer PV, Timm J, Liu D, Sitbon D, Boeri-Erba E, Velours C, et al. (March 2017). "Insights into the molecular architecture and histone H3-H4 deposition mechanism of yeast Chromatin assembly factor 1". eLife. 6: e23474. doi:10.7554/elife.23474. PMC 5404918. PMID 28315525.
  7. ^ Mattiroli F, Gu Y, Yadav T, Balsbaugh JL, Harris MR, Findlay ES, et al. (March 2017). "DNA-mediated association of two histone-bound complexes of yeast Chromatin Assembly Factor-1 (CAF-1) drives tetrasome assembly in the wake of DNA replication". eLife. 6: e22799. doi:10.7554/eLife.22799. PMC 5404915. PMID 28315523.
  8. ^ Zhang Z, Shibahara K, Stillman B (November 2000). "PCNA connects DNA replication to epigenetic inheritance in yeast". Nature. 408 (6809): 221–225. Bibcode:2000Natur.408..221Z. doi:10.1038/35041601. PMID 11089978. S2CID 205010657.
  9. ^ Houlard M, Berlivet S, Probst AV, Quivy JP, Héry P, Almouzni G, Gérard M (November 2006). "CAF-1 is essential for heterochromatin organization in pluripotent embryonic cells". PLOS Genetics. 2 (11): e181. doi:10.1371/journal.pgen.0020181. PMC 1630711. PMID 17083276.
  10. ^ Ishiuchi T, Enriquez-Gasca R, Mizutani E, Bošković A, Ziegler-Birling C, Rodriguez-Terrones D, et al. (September 2015). "Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly". Nature Structural & Molecular Biology. 22 (9): 662–671. doi:10.1038/nsmb.3066. PMID 26237512. S2CID 837230.
  11. ^ Funakoshi Y, Doi Y, Hosoda N, Uchida N, Osawa M, Shimada I, et al. (December 2007). "Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases". Genes & Development. 21 (23): 3135–3148. doi:10.1101/gad.1597707. PMC 2081979. PMID 18056425.

Further reading edit

  • Cheloufi S, Elling U, Hopfgartner B, Jung YL, Murn J, Ninova M, et al. (December 2015). "The histone chaperone CAF-1 safeguards somatic cell identity". Nature. 528 (7581): 218–224. Bibcode:2015Natur.528..218C. doi:10.1038/nature15749. PMC 4866648. PMID 26659182.
    • "Memory loss enables the production of stem cells". ScienceDaily (Press release). December 9, 2015.
  • Yu Z, Liu J, Deng WM, Jiao R (January 2015). "Histone chaperone CAF-1: essential roles in multi-cellular organism development". Cellular and Molecular Life Sciences. 72 (2): 327–337. doi:10.1007/s00018-014-1748-3. PMID 25292338. S2CID 18355941.
  • Kaufman PD (September 2015). "Want reprogramming? Cut back on the chromatin assembly!". Nature Structural & Molecular Biology. 22 (9): 648–650. doi:10.1038/nsmb.3081. PMID 26333710. S2CID 33569420.
  • Polo SE, Almouzni G (December 2015). "Chromatin dynamics after DNA damage: The legacy of the access-repair-restore model". DNA Repair. 36: 114–121. doi:10.1016/j.dnarep.2015.09.014. PMC 5113751. PMID 26429064.
  • Wang Z, Wu R, Nie Q, Bouchonville KJ, Diasio RB, Offer SM (March 2021). "Chromatin assembly factor 1 suppresses epigenetic reprogramming toward adaptive drug resistance". Journal of the National Cancer Center. 1 (1): 15–22. doi:10.1016/j.jncc.2020.12.003. S2CID 234287367.
  • Sauer PV, Gu Y, Liu WH, Mattiroli F, Panne D, Luger K, Churchill ME (November 2018). "Mechanistic insights into histone deposition and nucleosome assembly by the chromatin assembly factor-1". Nucleic Acids Research. 46 (19): 9907–9917. doi:10.1093/nar/gky823. PMC 6212844. PMID 30239791.

October 28, 2023
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Chromatin assembly factor 1 CAF 1 is a protein complex including Chaf1a p150 Chaf1b p60 and p48 subunits in humans or Cac1 Cac2 and Cac3 respectively in yeast that assembles histone tetramers onto replicating DNA during the S phase of the cell cycle 1 2 3 4 Steps in nucleosome assembly CAF 1 is shown in yellow interacting with the H3 H4 tetramer Contents 1 Function 2 Roles 3 References 4 Further readingFunction editCAF 1 functions as a histone chaperone that mediates the first step in nucleosome formation by tetramerizing and depositing newly synthesized histone H3 H4 onto DNA rapidly behind replication forks 5 6 7 H3 and H4 are synthesized in the cytoplasm 4 Several studies have shown that the interaction between CAF 1 and PCNA proliferating cell nuclear antigen which stabilizes CAF 1 at replication forks is important for CAF 1 s role in nucleosome assembly 8 The three subunits work together to make the complex function The human subunit p150 interacts with PCNA which acts as a sliding clamp to help the CAF 1 complex interact with the DNA replication fork Additionally p150 along with PCNA performs nucleotide excision repair to fix any damaged DNA P60 interacts with ASF1a b which is a histone chaperone for H3 H4 p48 has roles outside of CAF 1 but when involved with the complex it binds to H4 4 p60 attracts ASF1a b which is a chaperone for H3 H4 and this is in the complex with p150 which interacts with PCNA to attach to the replication fork The CAF 1 complex adds the histones to the DNA ahead of the replication fork 4 A mutation in p150 that results in a loss of function would lead to double stranded breaks interruptions in the replication fork and translocations In p60 loss of function would mean the histone chaperone for H3 H4 would not interact with the complex A mutation like this in either subunit would result in loss of function for the CAF 1 complex as a whole However loss of function in p48 would alter how well the complex is able to chaperone chromatin but would not stop it as a whole 4 Roles editCAF 1 is required for the spatial organization and epigenetic marking of heterochromatin domains in pluripotent embryonic cells creating a cellular memory of somatic cell identity during cellular differentiation 9 Cells resembling 2 cell stage mouse embryos totipotent cells can be induced in vitro through downregulation of the chromatin assembly activity of CAF 1 in embryonic stem cells 10 CAF 1 forms a deadenylase complex with CCR4 Not which should not be confused with the unrelated CCR4 The CAF 1 CCR4 Not complex cooperates with the release factor eRF3 and PABPC1 to shorten the poly A tail of mRNA during translation 11 References edit Fang Dong Han Junhong 2020 11 06 Histone Mutations and Cancer Springer Nature ISBN 978 981 15 8104 5 Smith S Stillman B July 1989 Purification and characterization of CAF I a human cell factor required for chromatin assembly during DNA replication in vitro Cell 58 1 15 25 doi 10 1016 0092 8674 89 90398 X PMID 2546672 S2CID 10515064 Hoek M Stillman B October 2003 Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in vivo Proceedings of the National Academy of Sciences of the United States of America 100 21 12183 12188 Bibcode 2003PNAS 10012183H doi 10 1073 pnas 1635158100 PMC 218733 PMID 14519857 a b c d e Volk Andrew Crispino John D August 2015 The role of the chromatin assembly complex CAF 1 and its p60 subunit CHAF1b in homeostasis and disease Biochimica et Biophysica Acta BBA Gene Regulatory Mechanisms 1849 8 979 986 doi 10 1016 j bbagrm 2015 05 009 ISSN 0006 3002 PMC 4515380 PMID 26066981 Liu WH Roemer SC Zhou Y Shen ZJ Dennehey BK Balsbaugh JL et al September 2016 The Cac1 subunit of histone chaperone CAF 1 organizes CAF 1 H3 H4 architecture and tetramerizes histones eLife 5 e18023 doi 10 7554 eLife 18023 PMC 5045291 PMID 27690308 Sauer PV Timm J Liu D Sitbon D Boeri Erba E Velours C et al March 2017 Insights into the molecular architecture and histone H3 H4 deposition mechanism of yeast Chromatin assembly factor 1 eLife 6 e23474 doi 10 7554 elife 23474 PMC 5404918 PMID 28315525 Mattiroli F Gu Y Yadav T Balsbaugh JL Harris MR Findlay ES et al March 2017 DNA mediated association of two histone bound complexes of yeast Chromatin Assembly Factor 1 CAF 1 drives tetrasome assembly in the wake of DNA replication eLife 6 e22799 doi 10 7554 eLife 22799 PMC 5404915 PMID 28315523 Zhang Z Shibahara K Stillman B November 2000 PCNA connects DNA replication to epigenetic inheritance in yeast Nature 408 6809 221 225 Bibcode 2000Natur 408 221Z doi 10 1038 35041601 PMID 11089978 S2CID 205010657 Houlard M Berlivet S Probst AV Quivy JP Hery P Almouzni G Gerard M November 2006 CAF 1 is essential for heterochromatin organization in pluripotent embryonic cells PLOS Genetics 2 11 e181 doi 10 1371 journal pgen 0020181 PMC 1630711 PMID 17083276 Ishiuchi T Enriquez Gasca R Mizutani E Boskovic A Ziegler Birling C Rodriguez Terrones D et al September 2015 Early embryonic like cells are induced by downregulating replication dependent chromatin assembly Nature Structural amp Molecular Biology 22 9 662 671 doi 10 1038 nsmb 3066 PMID 26237512 S2CID 837230 Funakoshi Y Doi Y Hosoda N Uchida N Osawa M Shimada I et al December 2007 Mechanism of mRNA deadenylation evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases Genes amp Development 21 23 3135 3148 doi 10 1101 gad 1597707 PMC 2081979 PMID 18056425 Further reading editCheloufi S Elling U Hopfgartner B Jung YL Murn J Ninova M et al December 2015 The histone chaperone CAF 1 safeguards somatic cell identity Nature 528 7581 218 224 Bibcode 2015Natur 528 218C doi 10 1038 nature15749 PMC 4866648 PMID 26659182 Memory loss enables the production of stem cells ScienceDaily Press release December 9 2015 Yu Z Liu J Deng WM Jiao R January 2015 Histone chaperone CAF 1 essential roles in multi cellular organism development Cellular and Molecular Life Sciences 72 2 327 337 doi 10 1007 s00018 014 1748 3 PMID 25292338 S2CID 18355941 Kaufman PD September 2015 Want reprogramming Cut back on the chromatin assembly Nature Structural amp Molecular Biology 22 9 648 650 doi 10 1038 nsmb 3081 PMID 26333710 S2CID 33569420 Polo SE Almouzni G December 2015 Chromatin dynamics after DNA damage The legacy of the access repair restore model DNA Repair 36 114 121 doi 10 1016 j dnarep 2015 09 014 PMC 5113751 PMID 26429064 Wang Z Wu R Nie Q Bouchonville KJ Diasio RB Offer SM March 2021 Chromatin assembly factor 1 suppresses epigenetic reprogramming toward adaptive drug resistance Journal of the National Cancer Center 1 1 15 22 doi 10 1016 j jncc 2020 12 003 S2CID 234287367 Sauer PV Gu Y Liu WH Mattiroli F Panne D Luger K Churchill ME November 2018 Mechanistic insights into histone deposition and nucleosome assembly by the chromatin assembly factor 1 Nucleic Acids Research 46 19 9907 9917 doi 10 1093 nar gky823 PMC 6212844 PMID 30239791 Retrieved from https en wikipedia org w index php title Chromatin assembly factor 1 amp oldid 1136170332, wikipedia, wiki, book, books, library,

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