Replication stress interferes with histone recycling and predeposition marking of new histones

TY - JOUR

T1 - Replication stress interferes with histone recycling and predeposition marking of new histones

AU - Jasencakova, Zuzana

AU - Scharf, Annette N D

AU - Ask, Katrine

AU - Corpet, Armelle

AU - Imhof, Axel

AU - Almouzni, Geneviève

AU - Groth, Anja

N1 - Paper id:: 10.1016/j.molcel.2010.01.033

PY - 2010/3/12

Y1 - 2010/3/12

N2 - To restore chromatin on new DNA during replication, recycling of histones evicted ahead of the fork is combined with new histone deposition. The Asf1 histone chaperone, which buffers excess histones under stress, is a key player in this process. Yet how histones handled by human Asf1 are modified remains unclear. Here we identify marks on histones H3-H4 bound to Asf1 and changes induced upon replication stress. In S phase, distinct cytosolic and nuclear Asf1b complexes show ubiquitous H4K5K12diAc and heterogeneous H3 marks, including K9me1, K14ac, K18ac, and K56ac. Upon acute replication arrest, the predeposition mark H3K9me1 and modifications typical of chromatin accumulate in Asf1 complexes. In parallel, ssDNA is generated at replication sites, consistent with evicted histones being trapped with Asf1. During recovery, histones stored with Asf1 are rapidly used as replication resumes. This shows that replication stress interferes with predeposition marking and histone recycling with potential impact on epigenetic stability.

AB - To restore chromatin on new DNA during replication, recycling of histones evicted ahead of the fork is combined with new histone deposition. The Asf1 histone chaperone, which buffers excess histones under stress, is a key player in this process. Yet how histones handled by human Asf1 are modified remains unclear. Here we identify marks on histones H3-H4 bound to Asf1 and changes induced upon replication stress. In S phase, distinct cytosolic and nuclear Asf1b complexes show ubiquitous H4K5K12diAc and heterogeneous H3 marks, including K9me1, K14ac, K18ac, and K56ac. Upon acute replication arrest, the predeposition mark H3K9me1 and modifications typical of chromatin accumulate in Asf1 complexes. In parallel, ssDNA is generated at replication sites, consistent with evicted histones being trapped with Asf1. During recovery, histones stored with Asf1 are rapidly used as replication resumes. This shows that replication stress interferes with predeposition marking and histone recycling with potential impact on epigenetic stability.

KW - Acetylation

KW - Blotting, Western

KW - Cell Cycle Proteins

KW - Cell Nucleus

KW - Chromatin Assembly and Disassembly

KW - Cytosol

KW - DNA Replication

KW - DNA, Single-Stranded

KW - Hela Cells

KW - Histones

KW - Humans

KW - Methylation

KW - Nuclear Proteins

KW - Nucleosomes

KW - Protein Binding

KW - Protein Processing, Post-Translational

KW - S Phase

KW - Stress, Physiological

KW - Tandem Mass Spectrometry

KW - Time Factors

KW - Transfection

U2 - 10.1016/j.molcel.2010.01.033

DO - 10.1016/j.molcel.2010.01.033

M3 - Journal article

C2 - 20227376

SN - 1097-2765

VL - 37

SP - 736

EP - 743

JO - Molecular Cell

JF - Molecular Cell

IS - 5

ER -