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FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1

The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction...

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Autores principales: Morillo-Huesca, Macarena, Maya, Douglas, Muñoz-Centeno, Mari Cruz, Singh, Rakesh Kumar, Oreal, Vincent, Reddy, Gajjalaiahvari Ugander, Liang, Dun, Géli, Vincent, Gunjan, Akash, Chávez, Sebastián
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873916/
https://www.ncbi.nlm.nih.gov/pubmed/20502685
http://dx.doi.org/10.1371/journal.pgen.1000964
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author Morillo-Huesca, Macarena
Maya, Douglas
Muñoz-Centeno, Mari Cruz
Singh, Rakesh Kumar
Oreal, Vincent
Reddy, Gajjalaiahvari Ugander
Liang, Dun
Géli, Vincent
Gunjan, Akash
Chávez, Sebastián
author_facet Morillo-Huesca, Macarena
Maya, Douglas
Muñoz-Centeno, Mari Cruz
Singh, Rakesh Kumar
Oreal, Vincent
Reddy, Gajjalaiahvari Ugander
Liang, Dun
Géli, Vincent
Gunjan, Akash
Chávez, Sebastián
author_sort Morillo-Huesca, Macarena
collection PubMed
description The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3) in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNA–damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication.
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spelling pubmed-28739162010-05-25 FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1 Morillo-Huesca, Macarena Maya, Douglas Muñoz-Centeno, Mari Cruz Singh, Rakesh Kumar Oreal, Vincent Reddy, Gajjalaiahvari Ugander Liang, Dun Géli, Vincent Gunjan, Akash Chávez, Sebastián PLoS Genet Research Article The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3) in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNA–damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication. Public Library of Science 2010-05-20 /pmc/articles/PMC2873916/ /pubmed/20502685 http://dx.doi.org/10.1371/journal.pgen.1000964 Text en Morillo-Huesca et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Morillo-Huesca, Macarena
Maya, Douglas
Muñoz-Centeno, Mari Cruz
Singh, Rakesh Kumar
Oreal, Vincent
Reddy, Gajjalaiahvari Ugander
Liang, Dun
Géli, Vincent
Gunjan, Akash
Chávez, Sebastián
FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1
title FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1
title_full FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1
title_fullStr FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1
title_full_unstemmed FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1
title_short FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1
title_sort fact prevents the accumulation of free histones evicted from transcribed chromatin and a subsequent cell cycle delay in g1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873916/
https://www.ncbi.nlm.nih.gov/pubmed/20502685
http://dx.doi.org/10.1371/journal.pgen.1000964
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