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

Author:

Réthi-Nagy Zsuzsánna12ORCID,Ábrahám Edit13ORCID,Sinka Rita4ORCID,Juhász Szilvia5,Lipinszki Zoltán13ORCID

Affiliation:

1. MTA SZBK Lendület Laboratory of Cell Cycle Regulation, Institute of Biochemistry, HUN-REN Biological Research Centre, H-6726 Szeged, Hungary

2. Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary

3. National Laboratory for Biotechnology, Institute of Genetics, HUN-REN Biological Research Centre, H-6726 Szeged, Hungary

4. Department of Genetics, University of Szeged, H-6726 Szeged, Hungary

5. Institute of Biochemistry, HUN-REN Biological Research Centre, H-6726 Szeged, Hungary

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.

Funder

National Research, Development and Innovation Office

National Laboratory for Biotechnology Program

Ministry of Human Capacities of Hungary

Hungarian Academy of Sciences

Lendület Program

Publisher

MDPI AG

Subject

General Medicine

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