Nuclear compartmentalization at the G1/S transition plays a key role in DNA replication control.

Authors

Asami Oji, Kosuke Yusa, Izumi Noda, Takako Ichinose, Yoshiko Kondo, Ichiro Hiratani

Published in

Nature communications. Volume 17. Issue 1. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Upon entry into the G1 phase following mitosis, mammalian chromosomal DNA becomes spatially segregated into A and B compartments, which correspond closely to classic euchromatin and heterochromatin, respectively. The functional significance of this spatial segregation, however, has remained unexplored due to the lack of means to manipulate this level of chromosomal organization. Through a genome-wide loss-of-function CRISPR screen, we identify GINS4, a component of the replicative DNA helicase complex, as a factor essential for segregation of A and B compartments during the G1-to-S phase transition. Using GINS4 depletion experiments, we show that proper A/B compartment organization at the time of S-phase entry plays a key role in efficient DNA synthesis. Furthermore, DNA synthesis with attenuated A/B compartments is associated with defects in replication timing regulation. Our findings uncover a previously unrecognized role for GINS4 in regulating nuclear architecture and underscore the biological significance of nuclear compartmentalization in DNA replication control.

PMID:
42575893
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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