# The Shu complex interacts with the replicative helicase to prevent mutations and aberrant recombination

## TL;DR

The Shu complex interacts with replication machinery to prevent DNA damage-induced mutations and recombination during replication.

## Contribution

The study reveals that the Shu complex interacts with replication initiation complexes ORC and MCM to prevent DNA damage.

## Key findings

- The Shu complex binds to replication origins and interacts with the MCM and ORC complexes.
- The Shu complex interaction with replication complexes is essential for DNA damage resistance and preventing mutations.
- The interaction occurs independently of recombinase proteins Rad51 and Rad52.

## Abstract

Homologous recombination (HR) is important for DNA damage tolerance during replication. The yeast Shu complex, a conserved homologous recombination factor, prevents replication-associated mutagenesis. Here we examine how yeast cells require the Shu complex for coping with MMS-induced lesions during DNA replication. We find that Csm2, a subunit of the Shu complex, binds to autonomous-replicating sequences (ARS) in yeast. Further evolutionary studies reveal that the yeast and human Shu complexes have co-evolved with specific replication-initiation factors. The connection between the Shu complex and replication is underlined by the finding that the Shu complex interacts with the ORC and MCM complexes. For example, the Shu complex interacts, independent of other HR proteins, with the replication initiation complexes through the N-terminus of Psy3. Lastly, we show interactions between the Shu complex and the replication initiation complexes are essential for resistance to DNA damage, to prevent mutations and aberrant recombination events. In our model, the Shu complex interacts with the replication machinery to enable error-free bypass of DNA damage.

The yeast Shu complex is a conserved homologous recombination (HR) factor that prevents replication-associated mutagenesis. This work finds it to interact with the ORC and MCM replication initiation factors, facilitating error-free bypass of replicative DNA damage.

The Shu complex binds to replication origins, where it interacts with the MCM and ORC complexes.The Shu complex subunit Psy3, a Rad51 paralog, mediates interaction with MCM or ORC complex.This interaction is necessary and sufficient to confer DNA damage resistance, and to prevent mutations and aberrant recombination events.Shu-complex interaction with MCM and ORC complexes occurs independently of recombinase Rad51 and Rad52.

The Shu complex binds to replication origins, where it interacts with the MCM and ORC complexes.

The Shu complex subunit Psy3, a Rad51 paralog, mediates interaction with MCM or ORC complex.

This interaction is necessary and sufficient to confer DNA damage resistance, and to prevent mutations and aberrant recombination events.

Shu-complex interaction with MCM and ORC complexes occurs independently of recombinase Rad51 and Rad52.

Psy3-mediated interaction with ORC and MCM complexes targets the conserved homologous recombination factor Shu to replication origins and is necessary to confer DNA damage resistance.