Transcriptional repressor ZBTB1 promotes chromatin remodeling and translesion DNA synthesis

Hyungjin Kim; Donniphat Dejsuphong; Guillaume Adelmant; Raphael Ceccaldi; Kailin Yang; Jarrod A Marto; Alan D D'Andrea

doi:10.1016/j.molcel.2014.02.017

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Transcriptional repressor ZBTB1 promotes chromatin remodeling and translesion DNA synthesis

Journal article

Open access

Peer reviewed

Transcriptional repressor ZBTB1 promotes chromatin remodeling and translesion DNA synthesis

Hyungjin Kim, Donniphat Dejsuphong, Guillaume Adelmant, Raphael Ceccaldi, Kailin Yang, Jarrod A Marto and Alan D D'Andrea

Molecular cell, Vol.54(1), pp.107-118

04/10/2014

DOI: 10.1016/j.molcel.2014.02.017

PMCID: PMC3989074

PMID: 24657165

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Abstract

Timely DNA replication across damaged DNA is critical for maintaining genomic integrity. Translesion DNA synthesis (TLS) allows bypass of DNA lesions using error-prone TLS polymerases. The E3 ligase RAD18 is necessary for proliferating cell nuclear antigen (PCNA) monoubiquitination and TLS polymerase recruitment; however, the regulatory steps upstream of RAD18 activation are less understood. Here, we show that the UBZ4 domain-containing transcriptional repressor ZBTB1 is a critical upstream regulator of TLS. The UBZ4 motif is required for PCNA monoubiquitination and survival after UV damage. ZBTB1 associates with KAP-1, a transcriptional repressor whose phosphorylation relaxes chromatin after DNA damage. ZBTB1 depletion impairs formation of phospho-KAP-1 at UV damage sites and reduces RAD18 recruitment. Furthermore, phosphorylation of KAP-1 is necessary for efficient PCNA modification. We propose that ZBTB1 is required for localizing phospho-KAP-1 to chromatin and enhancing RAD18 accessibility. Collectively, our study implicates a ubiquitin-binding protein in orchestrating chromatin remodeling during DNA repair.

Animals

Binding Sites

Cell Nucleus - drug effects

Cell Nucleus - metabolism

Cell Nucleus - radiation effects

Cell Survival

Chickens

Chromatin Assembly and Disassembly

DNA - biosynthesis

DNA Damage

DNA Replication

DNA-Binding Proteins - metabolism

DNA-Directed DNA Polymerase - metabolism

Enzyme Inhibitors - pharmacology

HEK293 Cells

HeLa Cells

Humans

Nucleic Acid Synthesis Inhibitors

Phosphorylation

Proliferating Cell Nuclear Antigen - metabolism

Repressor Proteins - genetics

Repressor Proteins - metabolism

RNA Interference

Signal Transduction

Time Factors

Transfection

Tripartite Motif-Containing Protein 28

Ubiquitin-Protein Ligases

Ubiquitination

Ultraviolet Rays

Details

Title: Subtitle: Transcriptional repressor ZBTB1 promotes chromatin remodeling and translesion DNA synthesis
Creators: Hyungjin Kim - Dana-Farber Cancer Institute
Donniphat Dejsuphong - Dana-Farber Cancer Institute
Guillaume Adelmant - Dana-Farber Cancer Institute
Raphael Ceccaldi - Dana-Farber Cancer Institute
Kailin Yang - Dana-Farber Cancer Institute
Jarrod A Marto - Dana-Farber Cancer Institute
Alan D D'Andrea - Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: alan_dandrea@dfci.harvard.edu
Resource Type: Journal article
Publication Details: Molecular cell, Vol.54(1), pp.107-118
DOI: 10.1016/j.molcel.2014.02.017
PMID: 24657165
PMCID: PMC3989074
ISSN: 1097-2765
eISSN: 1097-4164
Grant note: R37HL52725 / NHLBI NIH HHS 2P01HL048546 / NHLBI NIH HHS R01DK43889 / NIDDK NIH HHS R01 DK043889 / NIDDK NIH HHS P01 HL048546 / NHLBI NIH HHS P01 NS047572 / NINDS NIH HHS R01 HL052725 / NHLBI NIH HHS P01NS047572 / NINDS NIH HHS
Language: English
Date published: 04/10/2014
Academic Unit: Radiation Oncology
Record Identifier: 9984696568902771

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