Human Fact complex and DNA double-strand break (repair) (WP5564)

Homo sapiens

Open in new tab Open in Newt (SBGN)
Download PNG Download SVG Download JSON Download GPML Learn more about Downloads

This pathway shows the molecular details on the human Fact complex and DNA double-strand break (repair). These processes are involved in the Tessadori-Bicknell-van Haaften syndrome 3 (TEBINVAD) - for an overview of this syndrome see WP5575.

For a description of pathway objects, see the WikiPathways Legend.

Authors

Jorinde Lohmann , Yuanyuan Duan , Friederike Ehrhart , and Egon Willighagen

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Rare Diseases

Annotations

Pathway Ontology

disease pathway DNA repair pathway

Disease Ontology

epilepsy

Participants
Query Drugst.One

Label Type Compact URI Comment
DNA Metabolite chebi:4705
DNA double-strand breaks (DSB) Metabolite chebi:61120
NBN GeneProduct ensembl:ENSG00000104320
MDC1 GeneProduct ensembl:ENSG00000137337
ATM GeneProduct ensembl:ENSG00000149311
RAD54L GeneProduct ensembl:ENSG00000085999
RAD51 GeneProduct ensembl:ENSG00000051180
RNF8 GeneProduct ensembl:ENSG00000112130
XRCC6 GeneProduct ensembl:ENSG00000196419
XRCC5 GeneProduct ensembl:ENSG00000079246
RNF168 GeneProduct ensembl:ENSG00000163961
SETD2 GeneProduct ensembl:ENSG00000181555
PRKDC GeneProduct ensembl:ENSG00000253729
NAP1L1 GeneProduct ensembl:ENSG00000187109
TP53BP1 GeneProduct ensembl:ENSG00000067369
SSRP1 GeneProduct ensembl:ENSG00000149136
SUPT16H GeneProduct ensembl:ENSG00000092201
NASP GeneProduct ensembl:ENSG00000132780
H2A Protein uniprot:B2R5B3
H2B Protein uniprot:B4DR52
H4 Protein uniprot:P62805
H3 Protein uniprot:B4E380
H1 Protein uniprot:Q02539

References

  1. Megabase chromatin domains involved in DNA double-strand breaks in vivo. Rogakou EP, Boon C, Redon C, Bonner WM. J Cell Biol. 1999 Sep 6;146(5):905–16. PubMed Europe PMC Scholia
  2. The architecture of the human Rad54-DNA complex provides evidence for protein translocation along DNA. Ristic D, Wyman C, Paulusma C, Kanaar R. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8454–60. PubMed Europe PMC Scholia
  3. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ. J Biol Chem. 2001 Nov 9;276(45):42462–7. PubMed Europe PMC Scholia
  4. Homologous DNA pairing by human recombination factors Rad51 and Rad54. Sigurdsson S, Van Komen S, Petukhova G, Sung P. J Biol Chem. 2002 Nov 8;277(45):42790–4. PubMed Europe PMC Scholia
  5. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. Lukas C, Melander F, Stucki M, Falck J, Bekker-Jensen S, Goldberg M, et al. EMBO J. 2004 Jul 7;23(13):2674–83. PubMed Europe PMC Scholia
  6. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP. Cell. 2005 Dec 29;123(7):1213–26. PubMed Europe PMC Scholia
  7. High-resolution structure of the native histone octamer. Wood CM, Nicholson JM, Lambert SJ, Chantalat L, Reynolds CD, Baldwin JP. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jun 1;61(Pt 6):541–5. PubMed Europe PMC Scholia
  8. Nuclear autoantigenic sperm protein (NASP), a linker histone chaperone that is required for cell proliferation. Richardson RT, Alekseev OM, Grossman G, Widgren EE, Thresher R, Wagner EJ, et al. J Biol Chem. 2006 Jul 28;281(30):21526–34. PubMed Europe PMC Scholia
  9. RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling. Stewart GS, Stankovic T, Byrd PJ, Wechsler T, Miller ES, Huissoon A, et al. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16910–5. PubMed Europe PMC Scholia
  10. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, et al. Cell. 2007 Nov 30;131(5):887–900. PubMed Europe PMC Scholia
  11. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK, Miller ES, et al. Cell. 2009 Feb 6;136(3):420–34. PubMed Europe PMC Scholia
  12. DNA-dependent protein kinase (DNA-PK)-dependent cisplatin-induced loss of nucleolar facilitator of chromatin transcription (FACT) and regulation of cisplatin sensitivity by DNA-PK and FACT. Dejmek J, Iglehart JD, Lazaro JB. Mol Cancer Res. 2009 Apr;7(4):581–91. PubMed Europe PMC Scholia
  13. Functional characterization of human nucleosome assembly protein 1-like proteins as histone chaperones. Okuwaki M, Kato K, Nagata K. Genes Cells. 2010 Jan;15(1):13–27. PubMed Europe PMC Scholia
  14. Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia. Devgan SS, Sanal O, Doil C, Nakamura K, Nahas SA, Pettijohn K, et al. Cell Death Differ. 2011 Sep;18(9):1500–6. PubMed Europe PMC Scholia
  15. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. O’Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, et al. Nature. 2012 Apr 4;485(7397):246–50. PubMed Europe PMC Scholia
  16. BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair. Chapman JR, Sossick AJ, Boulton SJ, Jackson SP. J Cell Sci. 2012 Aug 1;125(Pt 15):3529–34. PubMed Europe PMC Scholia
  17. RNF8 regulates assembly of RAD51 at DNA double-strand breaks in the absence of BRCA1 and 53BP1. Nakada S, Yonamine RM, Matsuo K. Cancer Res. 2012 Oct 1;72(19):4974–83. PubMed Europe PMC Scholia
  18. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. O’Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, et al. Science. 2012 Dec 21;338(6114):1619–22. PubMed Europe PMC Scholia
  19. Histone methyltransferase SETD2 coordinates FACT recruitment with nucleosome dynamics during transcription. Carvalho S, Raposo AC, Martins FB, Grosso AR, Sridhara SC, Rino J, et al. Nucleic Acids Res. 2013 Mar 1;41(5):2881–93. PubMed Europe PMC Scholia
  20. Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. Machida S, Takaku M, Ikura M, Sun J, Suzuki H, Kobayashi W, et al. Sci Rep. 2014 May 6;4:4863. PubMed Europe PMC Scholia
  21. SETD2 is required for DNA double-strand break repair and activation of the p53-mediated checkpoint. Carvalho S, Vítor AC, Sridhara SC, Martins FB, Raposo AC, Desterro JMP, et al. Elife. 2014 May 6;3:e02482. PubMed Europe PMC Scholia
  22. Mutations in SETD2 cause a novel overgrowth condition. Luscan A, Laurendeau I, Malan V, Francannet C, Odent S, Giuliano F, et al. J Med Genet. 2014 Aug;51(8):512–7. PubMed Europe PMC Scholia
  23. Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy. Scheidecker S, Etard C, Haren L, Stoetzel C, Hull S, Arno G, et al. Am J Hum Genet. 2015 Apr 2;96(4):666–74. PubMed Europe PMC Scholia
  24. Brief Report: SETD2 Mutation in a Child with Autism, Intellectual Disabilities and Epilepsy. Lumish HS, Wynn J, Devinsky O, Chung WK. J Autism Dev Disord. 2015 Nov;45(11):3764–70. PubMed Europe PMC Scholia
  25. Integrated molecular mechanism directing nucleosome reorganization by human FACT. Tsunaka Y, Fujiwara Y, Oyama T, Hirose S, Morikawa K. Genes Dev. 2016 Mar 15;30(6):673–86. PubMed Europe PMC Scholia
  26. Structure/Function Analysis of Recurrent Mutations in SETD2 Protein Reveals a Critical and Conserved Role for a SET Domain Residue in Maintaining Protein Stability and Histone H3 Lys-36 Trimethylation. Hacker KE, Fahey CC, Shinsky SA, Chiang YCJ, DiFiore JV, Jha DK, et al. J Biol Chem. 2016 Sep 30;291(40):21283–95. PubMed Europe PMC Scholia
  27. Two novel cases expanding the phenotype of SETD2-related overgrowth syndrome. van Rij MC, Hollink IHIM, Terhal PA, Kant SG, Ruivenkamp C, van Haeringen A, et al. Am J Med Genet A. 2018 May;176(5):1212–5. PubMed Europe PMC Scholia
  28. Redefining the Etiologic Landscape of Cerebellar Malformations. Aldinger KA, Timms AE, Thomson Z, Mirzaa GM, Bennett JT, Rosenberg AB, et al. Am J Hum Genet. 2019 Sep 5;105(3):606–15. PubMed Europe PMC Scholia
  29. De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities. Bina R, Matalon D, Fregeau B, Tarsitano JJ, Aukrust I, Houge G, et al. J Med Genet. 2020 Jul;57(7):461–5. PubMed Europe PMC Scholia
  30. Exome sequencing improves genetic diagnosis of fetal increased nuchal translucency. Yang X, Huang LY, Pan M, Xu LL, Zhen L, Han J, et al. Prenat Diagn. 2020 Oct;40(11):1426–31. PubMed Europe PMC Scholia
  31. Genotype-phenotype correlation at codon 1740 of SETD2. Rabin R, Radmanesh A, Glass IA, Dobyns WB, Aldinger KA, Shieh JT, et al. Am J Med Genet A. 2020 Sep;182(9):2037–48. PubMed Europe PMC Scholia
  32. Structural basis of nucleosome dynamics modulation by histone variants H2A.B and H2A.Z.2.2. Zhou M, Dai L, Li C, Shi L, Huang Y, Guo Z, et al. EMBO J. 2021 Jan 4;40(1):e105907. PubMed Europe PMC Scholia
  33. Mutation pattern and genotype-phenotype correlations of SETD2 in neurodevelopmental disorders. Chen M, Quan Y, Duan G, Wu H, Bai T, Wang Y, et al. Eur J Med Genet. 2021 May;64(5):104200. PubMed Europe PMC Scholia
  34. Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations. Liu Y, Zhang Y, Xue H, Cao M, Bai G, Mu Z, et al. Cell Discov. 2021 May 11;7(1):32. PubMed Europe PMC Scholia
  35. A novel SETD2 variant causing global development delay without overgrowth in a Chinese 3-year-old boy. Wu Y, Liu F, Wan R, Jiao B. Front Genet. 2023 Mar 21;14:1153284. PubMed Europe PMC Scholia