New histone supply regulates replication fork speed and PCNA unloading
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New histone supply regulates replication fork speed and PCNA unloading. / Mejlvang, Jakob; Feng, Yunpeng; Alabert, Constance; Neelsen, Kai J; Jasencakova, Zusana; Zhao, Xiaobei; Lees, Michael; Sandelin, Albin; Pasero, Philippe; Lopes, Massimo; Groth, Anja.
In: Journal of Cell Biology, Vol. 204, No. 1, 06.01.2014, p. 29-43.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - New histone supply regulates replication fork speed and PCNA unloading
AU - Mejlvang, Jakob
AU - Feng, Yunpeng
AU - Alabert, Constance
AU - Neelsen, Kai J
AU - Jasencakova, Zusana
AU - Zhao, Xiaobei
AU - Lees, Michael
AU - Sandelin, Albin
AU - Pasero, Philippe
AU - Lopes, Massimo
AU - Groth, Anja
PY - 2014/1/6
Y1 - 2014/1/6
N2 - 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.
AB - 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.
U2 - 10.1083/jcb.201305017
DO - 10.1083/jcb.201305017
M3 - Journal article
C2 - 24379417
VL - 204
SP - 29
EP - 43
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 1
ER -
ID: 101191720