REAL

Protein Phosphatase 4 Is Required for Centrobin Function in DNA Damage Repair

Réthi-Nagy, Zsuzsánna and Ábrahám, Edit and Sinka, Rita and Juhász, Szilvia and Lipinszki, Zoltán (2023) Protein Phosphatase 4 Is Required for Centrobin Function in DNA Damage Repair. CELLS, 12 (18). No-2219. ISSN 2073-4409

[img]
Preview
Text
cells-12-02219.pdf
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

Genome stability in human cells relies on the efficient repair of double-stranded DNA breaks, which is mainly achieved by homologous recombination (HR). Among the regulators of various cellular functions, Protein phosphatase 4 (PP4) plays a pivotal role in coordinating cellular response to DNA damage. Meanwhile, Centrobin (CNTRB), initially recognized for its association with centrosomal function and microtubule dynamics, has sparked interest due to its potential contribution to DNA repair processes. In this study, we investigate the involvement of PP4 and its interaction with CNTRB in HR-mediated DNA repair in human cells. Employing a range of experimental strategies, we investigate the physical interaction between PP4 and CNTRB and shed light on the importance of two specific motifs in CNTRB, the PP4-binding FRVP and the ATR kinase recognition SQ sequences, in the DNA repair process. Moreover, we examine cells depleted of PP4 or CNTRB and cells harboring FRVP and SQ mutations in CNTRB, which result in similar abnormal chromosome morphologies. This phenomenon likely results from the impaired resolution of Holliday junctions, which serve as crucial intermediates in HR. Taken together, our results provide new insights into the intricate mechanisms of PP4 and CNTRB-regulated HR repair and their interrelation.

Item Type: Article
Uncontrolled Keywords: protein phosphatase 4; Centrobin; DNA damage response; homologous recombination, repair; arms-closed chromosome morphology; DNA double-stranded break
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
Q Science / természettudomány > QH Natural history / természetrajz > QH426 Genetics / genetika, örökléstan
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 26 Sep 2023 13:15
Last Modified: 26 Sep 2023 13:15
URI: http://real.mtak.hu/id/eprint/175089

Actions (login required)

Edit Item Edit Item