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. 2021 Mar 12;12:1626. doi: 10.1038/s41467-021-21878-x

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — a Western blots for MUS81 and MCM10. Quantification normalized to tubulin relative to the wild type sample is indicated. b Average proliferation rate in HCT116 wild type, MUS81^-/-, MCM10^+/- and double mutant cell lines normalized to HCT116 wild type, n = 6. Individual data points are indicated (gray circles). c Comparison of clonogenic survival of HCT116 wild type, MUS81^-/-, MCM10^+/- and double mutant cell lines. d Average percentage of each population represented by early apoptotic, late apoptotic or dead cells in HCT116 wild-type, MUS81^-/-, MCM10^+/- and double mutant cell lines, n = 2 replicates for HCT116 wild type and MCM10^+/- single mutants; n = 4 for all MUS81^-/- cell lines. Individual data points are indicated (gray circles). e TRF analysis of early passage HCT116 wild type, MUS81^-/-, MCM10^+/- and double mutant cell lines. Location of peak intensity (yellow dots) is indicated. f β-gal activity expressed as arbitrary fluorescence units normalized to total protein for MUS81^-/- (black) and MUS81^-/-, MCM10^+/- mutant cell lines (gray). Average levels for HCT116 wild type and MCM10^+/- cell lines from Supplementary Fig. 3d are indicated with dashed lines, n = 3. Individual data points are indicated (gray circles). Error bars in b, d, and f indicate SD and significance was calculated using an unpaired, two-tailed students t-test with *<0.05; **<0.01, ***<0.001. Source data for panels a, b, d, e, and f, including relevant exact p-values, are provided in the Source Data file. g Model of MCM10-associated telomeropathies. Different cell lineages have an inherent developmental threshold for MCM10 expression to achieve complete development and differentiation. As mono- or bi-allelic variants decrease the amount of functional MCM10, telomere erosion is accelerated. When MCM10 function is reduced below the required threshold, eroded telomeres cause replicative senescence and prevent complete development.