# The zinc finger of DNA Ligase 3α binds to nucleosomes via an arginine anchor

## TL;DR

This study shows how DNA Ligase 3α binds to nucleosomes using an arginine anchor, improving understanding of DNA repair mechanisms.

## Contribution

The discovery of a novel arginine anchor in LIG3α that enables binding to nucleosomes.

## Key findings

- LIG3α has higher affinity for nicks than XRCC1.
- LIG3α binds more strongly to undamaged nucleosomes than to single strand breaks in naked DNA.
- Binding to nucleosomes depends on two arginine residues in the N-terminal zinc finger.

## Abstract

Ligation of DNA single strand breaks is critical for maintaining genome integrity during DNA replication and repair. DNA Ligase III (LIG3α) forms an important complex with X-ray cross complementing protein 1 (XRCC1) during single strand break and base excision repair. We utilized a real time single molecule approach to quantify DNA binding kinetics of Halo-tagged LIG3α and XRCC1-YFP from nuclear extracts on long DNA substrates containing nicks, nucleosomes or nicks embedded in nucleosomes. LIG3α displayed higher affinity for nicks than XRCC1 with the LIG3α catalytic core and N-terminal zinc finger (ZnF) competing for nick engagement. Surprisingly, compared to single strand breaks in naked DNA, LIG3α bound even more avidly to an undamaged nucleosome reconstituted on the 601-sequence, with binding dependent on two arginine residues in the N-terminal ZnF. These studies reveal insights into nick detection and identify the role of a novel arginine anchor in LIG3α for engaging nucleosomes.