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Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion

Replication fork-associated factors promote genome integrity and protect against cancer. Mutations in the DDX11 helicase and the ESCO2 acetyltransferase also cause related developmental disorders classified as cohesinopathies. Here we generated vertebrate model cell lines of these disorders and cohe...

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Autores principales: Abe, Takuya, Kawasumi, Ryotaro, Arakawa, Hiroshi, Hori, Tetsuya, Shirahige, Katsuhiko, Losada, Ana, Fukagawa, Tatsuo, Branzei, Dana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356530/
https://www.ncbi.nlm.nih.gov/pubmed/27636994
http://dx.doi.org/10.18632/oncotarget.11982
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author Abe, Takuya
Kawasumi, Ryotaro
Arakawa, Hiroshi
Hori, Tetsuya
Shirahige, Katsuhiko
Losada, Ana
Fukagawa, Tatsuo
Branzei, Dana
author_facet Abe, Takuya
Kawasumi, Ryotaro
Arakawa, Hiroshi
Hori, Tetsuya
Shirahige, Katsuhiko
Losada, Ana
Fukagawa, Tatsuo
Branzei, Dana
author_sort Abe, Takuya
collection PubMed
description Replication fork-associated factors promote genome integrity and protect against cancer. Mutations in the DDX11 helicase and the ESCO2 acetyltransferase also cause related developmental disorders classified as cohesinopathies. Here we generated vertebrate model cell lines of these disorders and cohesinopathies-related genes. We found that vertebrate DDX11 and Tim-Tipin are individually needed to compensate for ESCO2 loss in chromosome segregation, with DDX11 also playing complementary roles with ESCO2 in centromeric cohesion. Our study reveals that overt centromeric cohesion loss does not necessarily precede chromosome missegregation, while both these problems correlate with, and possibly originate from, inner-centromere defects involving reduced phosphorylation of histone H3T3 (pH3T3) in the region. Interestingly, the mitotic pH3T3 mark was defective in all analyzed replication-related mutants with functions in cohesion. The results pinpoint mitotic pH3T3 as a postreplicative chromatin mark that is sensitive to replication stress and conducts with different kinetics to robust centromeric cohesion and correct chromosome segregation.
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spelling pubmed-53565302017-03-24 Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion Abe, Takuya Kawasumi, Ryotaro Arakawa, Hiroshi Hori, Tetsuya Shirahige, Katsuhiko Losada, Ana Fukagawa, Tatsuo Branzei, Dana Oncotarget Research Paper: Chromosome Replication fork-associated factors promote genome integrity and protect against cancer. Mutations in the DDX11 helicase and the ESCO2 acetyltransferase also cause related developmental disorders classified as cohesinopathies. Here we generated vertebrate model cell lines of these disorders and cohesinopathies-related genes. We found that vertebrate DDX11 and Tim-Tipin are individually needed to compensate for ESCO2 loss in chromosome segregation, with DDX11 also playing complementary roles with ESCO2 in centromeric cohesion. Our study reveals that overt centromeric cohesion loss does not necessarily precede chromosome missegregation, while both these problems correlate with, and possibly originate from, inner-centromere defects involving reduced phosphorylation of histone H3T3 (pH3T3) in the region. Interestingly, the mitotic pH3T3 mark was defective in all analyzed replication-related mutants with functions in cohesion. The results pinpoint mitotic pH3T3 as a postreplicative chromatin mark that is sensitive to replication stress and conducts with different kinetics to robust centromeric cohesion and correct chromosome segregation. Impact Journals LLC 2016-09-12 /pmc/articles/PMC5356530/ /pubmed/27636994 http://dx.doi.org/10.18632/oncotarget.11982 Text en Copyright: © 2016 Abe et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Chromosome
Abe, Takuya
Kawasumi, Ryotaro
Arakawa, Hiroshi
Hori, Tetsuya
Shirahige, Katsuhiko
Losada, Ana
Fukagawa, Tatsuo
Branzei, Dana
Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion
title Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion
title_full Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion
title_fullStr Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion
title_full_unstemmed Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion
title_short Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion
title_sort chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion
topic Research Paper: Chromosome
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356530/
https://www.ncbi.nlm.nih.gov/pubmed/27636994
http://dx.doi.org/10.18632/oncotarget.11982
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