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ATAD5 suppresses centrosome over-duplication by regulating UAF1 and ID1

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Title
ATAD5 suppresses centrosome over-duplication by regulating UAF1 and ID1
Author(s)
Seong-jung Kim; Minwoo Wie; Su Hyung Park; Tae Moon Kim; Jun Hong Park; Shinseog Kim; Kyungjae Myung; Kyoo-young Lee
Subject
ATAD5, ; Centrosome duplication, ; ID1, ; UAF1
Publication Date
2020-08
Journal
CELL CYCLE, v.19, no.15, pp.1952 - 1968
Publisher
TAYLOR & FRANCIS INC
Abstract
© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Centrosomes are the primary microtubule-organizing centers that are important for mitotic spindle assembly. Centrosome amplification is commonly observed in human cancer cells and contributes to genomic instability. However, it is not clear how centrosome duplication is dysregulated in cancer cells. Here, we report that ATAD5, a replisome protein that unloads PCNA from chromatin as a replication factor C-like complex (RLC), plays an important role in regulating centrosome duplication. ATAD5 is present at the centrosome, specifically at the base of the mother and daughter centrioles that undergo duplication. UAF1, which interacts with ATAD5 and regulates PCNA deubiquitination as a complex with ubiquitin-specific protease 1, is also localized at the centrosome. Depletion of ATAD5 or UAF1 increases cells with over-duplicated centrosome whereas ATAD5 overexpression reduces such cells. Consistently, the proportion of cells showing the multipolar mode of chromosome segregation is increased among ATAD5-depleted cells. The localization and function of ATAD5 at the centrosomes do not require other RLC subunits. UAF1 interacts and co-localizes with ID1, a protein that increases centrosome amplification upon overexpression. ATAD5 depletion reduces interactions between UAF1 and ID1 and increases ID1 signal at the centrosome, providing a mechanistic framework for understanding the role of ATAD5 in centrosome duplication
URI
https://pr.ibs.re.kr/handle/8788114/7711
DOI
10.1080/15384101.2020.1785724
ISSN
1538-4101
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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