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

Abstract

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.