Abstract
Correct duplication of DNA sequence and its organization into chromatin is central to genome function and stability. However, it remains unclear how cells coordinate DNA synthesis with provision of new histones for chromatin assembly to ensure chromosomal stability. In this paper, we show that replication fork speed is dependent on new histone supply and efficient nucleosome assembly. Inhibition of canonical histone biosynthesis impaired replication fork progression and reduced nucleosome occupancy on newly synthesized DNA. Replication forks initially remained stable without activation of conventional checkpoints, although prolonged histone deficiency generated DNA damage. PCNA accumulated on newly synthesized DNA in cells lacking new histones, possibly to maintain opportunity for CAF-1 recruitment and nucleosome assembly. Consistent with this, in vitro and in vivo analysis showed that PCNA unloading is delayed in the absence of nucleosome assembly. We propose that coupling of fork speed and PCNA unloading to nucleosome assembly provides a simple mechanism to adjust DNA replication and maintain chromatin integrity during transient histone shortage.
Original language | English |
---|---|
Pages (from-to) | 29-43 |
Number of pages | 15 |
Journal | Journal of Cell Biology |
Volume | 204 |
Issue number | 1 |
Early online date | 30 Dec 2013 |
DOIs | |
Publication status | Published - 6 Jan 2014 |
ASJC Scopus subject areas
- Cell Biology
Fingerprint
Dive into the research topics of 'New histone supply regulates replication fork speed and PCNA unloading'. Together they form a unique fingerprint.Profiles
-
Alabert, Constance
- Molecular Cell and Developmental Biology - Principal Investigator/Senior Lecturer (Teaching and Research)
Person: Academic