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PreprintCited by 8DNA Repair MechanismsGenomics and Chromatin DynamicsMicrotubule and mitosis dynamics

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Co-Essentiality Analysis Identifies PRR12 as a Regulator of Cohesin and Genome Integrity

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Nguyen, Alexandra L., Smith, Eric, Cheeseman, Iain M.·2024·Developmental Cell
DOI 10.1101/2024.03.29.587394PMC PMC12014375

Preprint — published as 10.1016/j.devcel.2024.12.015

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Abstract

Summary: The cohesin complex is critical for genome regulation, relying on specialized co-factors to mediate its diverse functional activities. Here, by analyzing patterns of similar gene requirements across cell lines, we identify PRR12 as a regulator of cohesin and genome integrity. We show that PRR12 interacts with cohesin and PRR12 loss results in a reduction of nuclear-localized cohesin and an accumulation of DNA lesions. We find that different cell lines across human and mouse exhibit significant variation in their sensitivity to PRR12 loss. Unlike the modest phenotypes observed in human cell lines, PRR12 depletion in mouse cells results in substantial genome instability. Despite a modest requirement in human cell lines, mutations in PRR12 lead to severe developmental defects in human patients, suggesting context-specific roles in cohesin regulation. By harnessing comparative studies across species and cell lines, our work reveals critical insights into how cohesin is regulated across diverse cellular contexts.

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Research works printed but not linked: 83

  1. 10.1016/j.cell.2014.11.021 · DOI · Paper page
  2. 10.1146/annurev-genet-102108-134233 · DOI
  3. 10.1038/nrg1110 · DOI
  4. 10.1083/jcb.200111002 · DOI
  5. 10.1016/S1097-2765(02)00515-4 · DOI
  6. 10.1146/annurev.biochem.74.082803.133219 · DOI
  7. 10.1083/jcb.150.3.405 · DOI
  8. 10.1371/journal.pone.0069458 · DOI
  9. 10.1016/j.gde.2020.02.024 · DOI
  10. 10.1016/j.cub.2018.05.019 · DOI
  11. 10.1101/gad.249202 · DOI
  12. 10.1016/j.tcb.2021.03.005 · DOI
  13. 2020, Shaping of the 3D genome by the ATPase machine cohesin, Exp Mol Med, 52, 1891, 10.1038/s12276-020-00526-2 · DOI
  14. 10.1038/nature06634 · DOI · Paper page
  15. 10.1126/science.aaz3418 · DOI · Paper page
  16. 10.1126/science.aaz4475 · DOI · Paper page
  17. 10.1016/j.bbrc.2006.01.029 · DOI
  18. 10.1016/j.molcel.2006.08.018 · DOI
  19. 10.1242/jcs.011999 · DOI
  20. 10.1534/genetics.103.024851 · DOI
  21. 10.1371/journal.pgen.1002574 · DOI
  22. 10.1002/bies.20691 · DOI
  23. 10.1016/j.molcel.2008.06.005 · DOI
  24. 10.1126/science.1140649 · DOI
  25. 10.1016/S0960-9822(01)00271-8 · DOI
  26. 10.1101/gad.1724308 · DOI
  27. 10.1016/j.cub.2006.03.049 · DOI · Paper page
  28. 10.1016/S1097-2765(00)80420-7 · DOI · Paper page
  29. 10.1038/ncb1177 · DOI
  30. 10.1016/j.cub.2004.07.053 · DOI
  31. 2021, Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism, Cell, 184, 5448, 10.1016/j.cell.2021.09.016 · DOI
  32. 10.1007/s00412-007-0104-x · DOI
  33. 10.3389/fgene.2012.00171 · DOI
  34. 2020, Chromatinopathies: A focus on Cornelia de Lange syndrome, Clin Genet, 97, 3, 10.1111/cge.13674 · DOI
  35. 10.1242/dev.090605 · DOI
  36. 10.1371/journal.pgen.1004153 · DOI
  37. 2021, Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome, Nat Commun, 12, 4551, 10.1038/s41467-021-24808-z · DOI
  38. 10.1186/s13148-017-0391-x · DOI
  39. 10.1016/j.bbadis.2013.07.020 · DOI
  40. 10.1093/hmg/ddn116 · DOI
  41. 10.1038/ng1548 · DOI
  42. 2021, A genome-wide atlas of co-essential modules assigns function to uncharacterized genes, Nat Genet, 53, 638, 10.1038/s41588-021-00840-z · DOI · Paper page
  43. 10.1073/pnas.1206840109 · DOI
  44. 10.1016/j.molcel.2018.05.022 · DOI
  45. 2023, Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2, Nat Commun, 14, 1326, 10.1038/s41467-023-36900-7 · DOI
  46. 10.1007/s00439-018-1877-0 · DOI
  47. 10.1007/s10048-015-0452-2 · DOI
  48. 2021, Dominant variants in PRR12 result in unilateral or bilateral complex microphthalmia, Clin Genet, 99, 437, 10.1111/cge.13897 · DOI
  49. 2021, Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities, Genet Med, 23, 1234, 10.1038/s41436-021-01129-6 · DOI
  50. 2010, Brachman de Lange syndrome, Contemp Clin Dent, 1, 268, 10.4103/0976-237X.76399 · DOI
  51. 10.1038/ng1364 · DOI · Paper page
  52. 10.1038/nature22063 · DOI · Paper page
  53. 10.1016/j.cub.2006.10.061 · DOI · Paper page
  54. Srinivasan, M. , et al., Scc2 counteracts a Wapl-independent mechanism that releases cohesin from chromosomes during G1. Elife, 2019. 8. · DOI
  55. 2006, A wapl a day keeps the sisters apart: wapl and cohesin dynamics, Dev Cell, 11, 754, 10.1016/j.devcel.2006.11.010 · DOI
  56. 10.1016/j.cell.2006.09.040 · DOI · Paper page
  57. Holzmann, J. , et al., Absolute quantification of cohesin, CTCF and their regulators in human cells. Elife, 2019. 8. · DOI
  58. 10.1074/jbc.RA119.007832 · DOI
  59. Evans, R. , et al., Protein complex prediction with AlphaFold-Multimer. bioRxiv, 2022: p. 2021.10.04.463034.
  60. 10.1016/j.febslet.2013.06.035 · DOI
  61. 10.15252/embj.201798004 · DOI · Paper page
  62. 2022, Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression, PLoS Genet, 18, e1010528, 10.1371/journal.pgen.1010528 · DOI
  63. 10.1016/j.dnarep.2007.07.017 · DOI
  64. 10.1016/j.molcel.2010.09.019 · DOI · Paper page
  65. 10.1038/363368a0 · DOI
  66. 10.1128/MCB.21.13.4129-4139.2001 · DOI · Paper page
  67. 10.1101/gad.14.12.1448 · DOI · Paper page
  68. 10.1371/journal.pgen.1002460 · DOI · Paper page
  69. 10.1074/jbc.M209123200 · DOI
  70. 10.1016/j.bbrc.2011.07.021 · DOI
  71. 10.1242/jcs.197236 · DOI
  72. 2022, Genome-wide CRISPR screens using isogenic cells reveal vulnerabilities conferred by loss of tumor suppressors, Sci Adv, 8, eabm6638, 10.1126/sciadv.abm6638 · DOI
  73. 10.1016/j.molcel.2020.07.010 · DOI
  74. 2021, Pooled CRISPR screening in pancreatic cancer cells implicates co-repressor complexes as a cause of multiple drug resistance via regulation of epithelial-to-mesenchymal transition, BMC Cancer, 21, 632, 10.1186/s12885-021-08388-1 · DOI
  75. 10.1371/journal.pgen.1009176 · DOI
  76. 10.1101/cshperspect.a016550 · DOI
  77. 10.1074/jbc.M112.400192 · DOI
  78. 10.1101/gad.608210 · DOI
  79. 10.1074/jbc.RA119.011099 · DOI
  80. 10.1038/s41467-019-09659-z · DOI
  81. 10.1016/j.cell.2017.01.013 · DOI · Paper page
  82. Keys, H.R. and K.A. Knouse , Genome-scale CRISPR screening in a single mouse liver. Cell Genom, 2022. 2(12). · DOI
  83. 10.1038/nmeth.3047 · DOI · Paper page

Metadata

Authors
Nguyen, A. L., Smith, E., & Cheeseman, I. M.
Affiliations
Whitehead Institute for Biomedical Research (US)
Corresponding author
Cheeseman, Iain M.
ORCID
Venue
Developmental Cell
Publisher
openRxiv
Published
2024-03-30
Volume
60
Issue
8
Pages
1217-1233.e7
ISSN
1534-5807 (ISSN-L)
DOI
10.1101/2024.03.29.587394
PMC
PMC12014375
OpenAlex
W4405943415
Cited by
8
References
1
Citations by year
2026: 2 · 2025: 6
FWCI
1.23
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (acceptedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (2029868)
  • American Cancer Society
  • Damon Runyon Cancer Research Foundation
  • National Institutes of Health
  • National Institute of General Medical Sciences (R35GM126930)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
cohesin, NIPBL, genome stability, DNA double-strand breaks, DNA damage response
MeSH terms
Cohesins, Animals, Chromosomal Proteins, Non-Histone, DNA Damage, HeLa Cells, Humans, Nuclear Proteins, Cell Cycle Proteins, NIH 3T3 Cells, Genomic Instability, Mice, DNA Breaks, Double-Stranded

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