# Influence of PARP1 on CRISPR/Cas9 induced double strand break repair in proliferating cells

## TL;DR

This study shows how PARP1 affects DNA repair pathways used in CRISPR/Cas9 genome editing, influencing the types of edits that occur.

## Contribution

The paper reveals that PARP1 modulation can shift DNA repair outcomes, offering a new strategy to improve genome editing precision.

## Key findings

- PARP1 downregulation increases both NHEJ and MMEJ repair without affecting HR.
- PARP1 overexpression reduces NHEJ and HR but does not impact MMEJ.
- Modulating PARP1 alters the balance of DNA repair pathways in CRISPR/Cas9 editing.

## Abstract

Genome editing with CRISPR/Cas9 depends on the induction of site-specific DNA double-strand breaks (DSBs), which are repaired by distinct pathways. Non-homologous end joining (NHEJ) frequently introduces insertions or deletions (indels), resulting in mutagenic repair, whereas microhomology-mediated end joining (MMEJ) produces larger deletions due to end resection. In the presence of a donor template, homologous recombination (HR) enables precise sequence changes but is generally inefficient in many cell types. Modulating the activity of key repair factors has therefore emerged as a promising strategy to bias DSB repair outcomes toward more predictable or precise edits. Here, we employed luminescent and fluorescent reporter assays to systematically quantify the impact of PARP1 modulation on repair pathway choice. We show that PARP1 downregulation increased both NHEJ and MMEJ repair without altering HR, while PARP1 overexpression reduced NHEJ and HR but left MMEJ activity unaffected. These results highlight PARP1 as a regulator of DSB repair balance and suggest that targeted modulation of PARP1 could improve the precision of CRISPR-based genome editing.

•PARP1 Modulates DNA Repair Pathway Choice.•PARP1 Overexpression Suppresses Mutagenic Repair.•PARP1 Depletion Enhances MMEJ but Also Promotes NHEJ.•HDR Efficiency Remains Unaffected by PARP1 Downregulation.

PARP1 Modulates DNA Repair Pathway Choice.

PARP1 Overexpression Suppresses Mutagenic Repair.

PARP1 Depletion Enhances MMEJ but Also Promotes NHEJ.

HDR Efficiency Remains Unaffected by PARP1 Downregulation.