Human ELG1 regulates the level of monoubiquitinated PCNA through interactions with PCNA, USP1, and polymerase η

Kyungjae Myung; Soma Banerjee; Kailin Yang; Nilabja Sikdar; Kyoo‐young Lee; Martin Cohn; Stephen Wincovitch; Evgenia Pak; Koji Nakanishi; Maria Jasin; Amalia Dutra; Alan D'Andrea

doi:10.1096/fasebj.23.1_supplement.836.2

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Human ELG1 regulates the level of monoubiquitinated PCNA through interactions with PCNA, USP1, and polymerase η

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Human ELG1 regulates the level of monoubiquitinated PCNA through interactions with PCNA, USP1, and polymerase η

Kyungjae Myung, Soma Banerjee, Kailin Yang, Nilabja Sikdar, Kyoo‐young Lee, Martin Cohn, Stephen Wincovitch, Evgenia Pak, Koji Nakanishi, Maria Jasin, …

The FASEB journal, Vol.23(S1), pp.836.2-836.2

04/2009

DOI: 10.1096/fasebj.23.1_supplement.836.2

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Abstract

Abstract only The level of monoubiquitinated PCNA in chromatin is closely linked with DNA damage bypass during DNA replication. However, it remains unclear how the level of monoubiquitinated PCNA in chromatin is regulated. Here, we demonstrate that human ELG1 (hELG1) regulates the level of monoubiquitinated PCNA in chromatin, through its interactions with PCNA, the tanslesion synthesis DNA polymerase η, and the deubiquitinating enzyme, USP1. The level of hELG1 is induced during recovery from DNA damage, resulting in the assembly of distinct hELG1 foci at stalled DNA replication forks. Furthermore, hELG1 foci start to appear where foci of DNA polymerase η exist. Targeted gene knockdown of hELG1 by shRNAs enhanced homologous recombination and resulted in genomic instabilities and hypersensitivity to DNA damaging agents. Taken together, hELG1 suppresses genomic instability by reducing monoubiquitinated PCNA from chromatin after DNA damage bypass through its interaction with and stabilization of USP1.

Details

Title: Subtitle: Human ELG1 regulates the level of monoubiquitinated PCNA through interactions with PCNA, USP1, and polymerase η
Creators: Kyungjae Myung - National Human Genome Research Institute
Soma Banerjee - National Human Genome Research Institute
Kailin Yang - Harvard Medical School
Nilabja Sikdar - National Human Genome Research Institute
Kyoo‐young Lee - National Human Genome Research Institute
Martin Cohn - Radiation Oncoboly Hovard Medical School Boston MA
Stephen Wincovitch - National Human Genome Research Institute
Evgenia Pak - National Human Genome Research Institute
Koji Nakanishi - Memorial Sloan Kettering Cancer Center
Maria Jasin - Memorial Sloan Kettering Cancer Center
Amalia Dutra - National Human Genome Research Institute
Alan D'Andrea - Radiation Oncoboly Hovard Medical School Boston MA
Resource Type: Abstract
Publication Details: The FASEB journal, Vol.23(S1), pp.836.2-836.2
DOI: 10.1096/fasebj.23.1_supplement.836.2
ISSN: 0892-6638
eISSN: 1530-6860
Language: English
Date published: 04/2009
Academic Unit: Radiation Oncology
Record Identifier: 9984696680802771

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