10779/crick.12546671.v1
Roberto Bellelli
Roberto
Bellelli
Ondrej Belan
Ondrej
Belan
Valerie E Pye
Valerie E
Pye
Camille Clement
Camille
Clement
Sarah L Maslen
Sarah L
Maslen
J Mark Skehel
J Mark
Skehel
Peter Cherepanov
Peter
Cherepanov
Genevieve Almouzni
Genevieve
Almouzni
Simon J Boulton
Simon J
Boulton
POLE3-POLE4 is a histone H3-H4 chaperone that maintains chromatin integrity during DNA replication
The Francis Crick Institute
2020
POLE3-POLE4 complex
epigenome stability
histone chaperone
replication-coupled nucleosome assembly
Chromatin
DNA Polymerase II
DNA Polymerase III
DNA Replication
DNA-Binding Proteins
Epigenesis, Genetic
Histone Chaperones
Histones
Humans
Molecular Chaperones
Nucleoproteins
Nucleosomes
Poly-ADP-Ribose Binding Proteins
Proliferating Cell Nuclear Antigen
Protein Binding
Boulton FC001048
Cherepanov FC001061
FC-ack
PC-ack
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
2020-06-26 09:41:47
Journal contribution
https://crick.figshare.com/articles/journal_contribution/POLE3-POLE4_is_a_histone_H3-H4_chaperone_that_maintains_chromatin_integrity_during_DNA_replication/12546671
Maintenance of epigenetic integrity relies on coordinated recycling and partitioning of parental histones and deposition of newly synthesized histones during DNA replication. This process depends upon a poorly characterized network of histone chaperones, remodelers, and binding proteins. Here we implicate the POLE3-POLE4 subcomplex of the leading-strand polymerase, PolĪµ, in replication-coupled nucleosome assembly through its ability to selectively bind to histones H3-H4. Using hydrogen/deuterium exchange mass spectrometry and physical mapping, we define minimal domains necessary for interaction between POLE3-POLE4 and histones H3-H4. Biochemical analyses establish that POLE3-POLE4 is a histone chaperone that promotes tetrasome formation and DNA supercoiling in vitro. In cells, POLE3-POLE4 binds both newly synthesized and parental histones, and its depletion hinders helicase unwinding and chromatin PCNA unloading and compromises coordinated parental histone retention and new histone deposition. Collectively, our study reveals that POLE3-POLE4 possesses intrinsic H3-H4 chaperone activity, which facilitates faithful nucleosome dynamics at the replication fork.