# The Rtt107 interactome structures and functions

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $395,120

## Abstract

Summary
 Complete genome duplication requires a close collaboration between the replication machinery and
many regulatory factors. These factors can assist replisomes in coping with large numbers of template
obstacles, and their defects are frequently associated with human diseases such as cancer and DNA damage
syndromes. It is our long-term goal to understand how replication regulatory proteins interact with the
replisome and aid replication. We and others have shown that the evolutionarily conserved Smc5/6 complex is
essential for promoting replication under normal and DNA damaging conditions. During the last two cycles of
this grant, we have made significant progress in elucidating the structure of this complex, its unique SUMO E3
activity, and its multiple effects on genome maintenance in the budding yeast model system.
 Importantly and most relevant to the current proposal, we recently showed that Smc5/6 and its binding
partner, the scaffold protein Rtt107, comprise a new pathway that aids large replicon synthesis. Large
replicons are difficult to duplicate and strongly associated with fragile sites and other forms of genomic
instability. Investigating the mechanisms by which Smc5/6 and Rtt107 facilitate large replicon synthesis will
broaden our understanding of the maintenance of high-risk genomic regions. We found that Smc5/6 and
Rtt107 interact with DNA polymerase and helicase complexes and contribute to their sumoylation. Moreover,
these sumoylation events influence replication. Based on these findings, we hypothesize that Smc5/6 and
Rtt107 directly promote replisome function to aid large replicon synthesis. Extending from this work, we
showed that Rtt107 is the hub of a protein network composed of Smc5/6 and other genome maintenance
factors. How Rtt107 supports the interactions within this network and how each interaction contributes to
replication are important questions to address.
 In the next funding cycle, we propose to test our hypothesis stated above by examining how Smc5/6
and Rtt107 affect replication fork functions during large replicon synthesis, and define the biochemical features
of the Smc5/6 and Rtt107 interactions with DNA polymerase and helicase complexes. In addition, we will
determine how the sumoylation of DNA polymerase and helicase complexes affects the initiation and
elongation stages of replication. Findings from these studies will shed light on the roles of Smc5/6, Rtt107, and
SUMO in promoting the completion of large replicon synthesis. Finally, we will investigate the biochemical
basis of Rtt107-mediated interactions and the functions of each interaction. To achieve these goals, we will use
a combination of genetic, biochemical, biophysical approaches in the highly effective yeast system. Outcomes
of the proposed work will expand our view on how large replicon synthesis is achieved, how SUMO regulates
replication, and how the Rtt107 interactome contributes to genome duplication. As such, these studies will
hav...

## Key facts

- **NIH application ID:** 10079485
- **Project number:** 5R01GM080670-13
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Xiaolan Zhao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,120
- **Award type:** 5
- **Project period:** 2007-09-20 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079485

## Citation

> US National Institutes of Health, RePORTER application 10079485, The Rtt107 interactome structures and functions (5R01GM080670-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10079485. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*