학술논문
DNA replication acts as an error correction mechanism to maintain centromere identity by restricting CENP-A to centromeres
Document Type
Academic Journal
Author
Source
Nature Cell Biology. June 2019, Vol. 21 Issue 6, p743, 12 p.
Subject
Language
English
ISSN
1465-7392
Abstract
Author(s): Yael Nechemia-Arbely [sup.1] [sup.4], Karen H. Miga [sup.2], Ofer Shoshani [sup.1], Aaron Aslanian [sup.3], Moira A. McMahon [sup.1] [sup.5], Ah Young Lee [sup.1], Daniele Fachinetti [sup.1] [sup.6], John R. [...]
Chromatin assembled with the histone H3 variant CENP-A is the heritable epigenetic determinant of human centromere identity. Using genome-wide mapping and reference models for 23 human centromeres, CENP-A binding sites are identified within the megabase-long, repetitive [alpha]-satellite DNAs at each centromere. CENP-A is shown in early G1 to be assembled into nucleosomes within each centromere and onto 11,390 transcriptionally active sites on the chromosome arms. DNA replication is demonstrated to remove ectopically loaded, non-centromeric CENP-A. In contrast, tethering of centromeric CENP-A to the sites of DNA replication through the constitutive centromere associated network (CCAN) is shown to enable precise reloading of centromere-bound CENP-A onto the same DNA sequences as in its initial prereplication loading. Thus, DNA replication acts as an error correction mechanism for maintaining centromere identity through its removal of non-centromeric CENP-A coupled with CCAN-mediated retention and precise reloading of centromeric CENP-A. Cleveland and colleagues report a DNA-replication-dependent error correction mechanism that acts in S phase to remove ectopically loaded CENP-A outside the centromeres, while retaining centromere-bound CENP-A.
Chromatin assembled with the histone H3 variant CENP-A is the heritable epigenetic determinant of human centromere identity. Using genome-wide mapping and reference models for 23 human centromeres, CENP-A binding sites are identified within the megabase-long, repetitive [alpha]-satellite DNAs at each centromere. CENP-A is shown in early G1 to be assembled into nucleosomes within each centromere and onto 11,390 transcriptionally active sites on the chromosome arms. DNA replication is demonstrated to remove ectopically loaded, non-centromeric CENP-A. In contrast, tethering of centromeric CENP-A to the sites of DNA replication through the constitutive centromere associated network (CCAN) is shown to enable precise reloading of centromere-bound CENP-A onto the same DNA sequences as in its initial prereplication loading. Thus, DNA replication acts as an error correction mechanism for maintaining centromere identity through its removal of non-centromeric CENP-A coupled with CCAN-mediated retention and precise reloading of centromeric CENP-A. Cleveland and colleagues report a DNA-replication-dependent error correction mechanism that acts in S phase to remove ectopically loaded CENP-A outside the centromeres, while retaining centromere-bound CENP-A.