Stabilization and targeting of INO80 to replication forks by BAP1 during normal DNA synthesis

Han Sae Lee, Shin Ai Lee, Shin Kyoung Hur, Jeong Wook Seo, Jongbum Kwon

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


The INO80 chromatin-remodelling complex has been implicated in DNA replication during stress in yeast. However, its role in normal DNA replication and its underlying mechanisms remain unclear. Here, we show that INO80 binds to replication forks and promotes fork progression in human cells under unperturbed, normal conditions. We find that Ino80, which encodes the catalytic ATPase of INO80, is essential for mouse embryonic DNA replication and development. Ino80 is recruited to replication forks through interaction with ubiquitinated H2A - aided by BRCA1-associated protein-1 (BAP1), a tumour suppressor and nuclear de-ubiquitinating enzyme that also functions to stabilize Ino80. Importantly, Ino80 is downregulated in BAP1-defective cancer cells due to the lack of an Ino80 stabilization mechanism via BAP1. Our results establish a role for INO80 in normal DNA replication and uncover a mechanism by which this remodeler is targeted to replication forks, suggesting a molecular basis for the tumour-suppressing function of BAP1.

Original languageEnglish
Article number5128
JournalNature Communications
StatePublished - 2014

Bibliographical note

Funding Information:
We thank Soo-Jong Um for providing the Flag-BAP1 expression vectors and Goo-Taeg Oh and Daekee Lee for help with the mouse experiments. This work was supported by the National Research Foundation grant funded by the Korea Ministry of Education and Science (NRF-2012R1A2A2A01003744), and the grant from the National R&D Program for Cancer Control, Korea Ministry for Health and Welfare (1020060) and partly by NRF-2010-0023376, NRF-2012R1A5A1048236 and the Ewha Global Top 5 Grant 2013.

Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.


Dive into the research topics of 'Stabilization and targeting of INO80 to replication forks by BAP1 during normal DNA synthesis'. Together they form a unique fingerprint.

Cite this