# RECQ5-dependent SUMO2 conjugation of PCNA in the resolution of transcription-replication conflicts

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2022 · $387,823

## Abstract

Project Summary
Proliferating cell nuclear antigen (PCNA) is an essential component of the replisome, and it enhances the
processivity of the DNA polymerases in DNA synthesis. In addition, in response to DNA damage, PCNA is
ubiquitinated at lysine 164 (K164) to bypass DNA lesions. In unperturbed cells, the same K164 residue can
also be conjugated with either SUMO1 or SUMO2, and SUMO1-PCNA has been implicated in recruiting PARI
helicase to suppress homologous recombination. However, the source of replication obstacle that triggers
PCNA SUMOylation is yet to be defined, and the regulators of PCNA SUMOylation are not known. It is also not
clear if SUMO2-PCNA functions redundantly to SUMO1-PCNA. Our newly published data argue that human
SUMO2-PCNA has a unique function in transcription that is not shared by SUMO1-PCNA, because only
SUMO2-PCNA is associated with transcriptionally active chromatin. Even though PCNA SUMO2 conjugation
occurs in S-phase, SUMO2-PCNA is induced by RNA polymerase II - dependent transcription and requires the
RNA polymerase II - interacting protein, RECQ5 DNA helicase. Importantly, cells with reduced SUMO2-PCNA
accumulate transcription-induced DNA double-strand breaks during S-phase. Therefore, our data support a
conceptually innovative model for a role of SUMO2-PCNA in resolving transcription-replication conflicts to
minimize genomic instability. The goal of this proposal is (1) to identify the molecular factors that facilitate the
transcription-induced SUMO2 conjugation of PCNA, (2) to identify the molecular mechanism by which SUMO2-
PCNA resolves transcription-replication conflicts, and (3) to elucidate the contribution of SUMO2-PCNA toward
preventing genomic instability and neoplastic transformation, as transcription-replication conflicts are major
source for common fragile site instability.

## Key facts

- **NIH application ID:** 10328909
- **Project number:** 5R01CA225843-04
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Yilun Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,823
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328909

## Citation

> US National Institutes of Health, RePORTER application 10328909, RECQ5-dependent SUMO2 conjugation of PCNA in the resolution of transcription-replication conflicts (5R01CA225843-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328909. Licensed CC0.

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