1. Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP.
- Author
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Zasadzińska E, Huang J, Bailey AO, Guo LY, Lee NS, Srivastava S, Wong KA, French BT, Black BE, and Foltz DR
- Subjects
- Centromere metabolism, Centromere Protein A genetics, Chromatin metabolism, Chromatin Assembly and Disassembly physiology, Chromosomal Proteins, Non-Histone metabolism, Chromosome Segregation physiology, DNA Replication, DNA-Binding Proteins genetics, Epigenomics, HEK293 Cells, HeLa Cells, Histones metabolism, Humans, Kinetochores metabolism, Mitosis physiology, Nucleosomes genetics, S Phase, Centromere Protein A metabolism, DNA-Binding Proteins metabolism, Nucleosomes metabolism
- Abstract
Centromeric chromatin defines the site of kinetochore formation and ensures faithful chromosome segregation. Centromeric identity is epigenetically specified by the incorporation of CENP-A nucleosomes. DNA replication presents a challenge for inheritance of centromeric identity because nucleosomes are removed to allow for replication fork progression. Despite this challenge, CENP-A nucleosomes are stably retained through S phase. We used BioID to identify proteins transiently associated with CENP-A during DNA replication. We found that during S phase, HJURP transiently associates with centromeres and binds to pre-existing CENP-A, suggesting a distinct role for HJURP in CENP-A retention. We demonstrate that HJURP is required for centromeric nucleosome inheritance during S phase. HJURP co-purifies with the MCM2-7 helicase complex and, together with the MCM2 subunit, binds CENP-A simultaneously. Therefore, pre-existing CENP-A nucleosomes require an S phase function of the HJURP chaperone and interaction with MCM2 to ensure faithful inheritance of centromere identity through DNA replication., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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