# Molecular mechanisms of genome maintenance during DNA replication and repair

> **NIH NIH K00** · STANFORD UNIVERSITY · 2020 · $92,233

## Abstract

Project Summary
DNA replication is a fundamental process that includes the accurate duplication of the genome as well as the
re-establishment of chromatin modifications and epigenetic information. DNA damage interferes with
replication fidelity, leading to an accumulation of mutations and chromosomal translocations, which cause
genome instability. The DNA damage response (DDR) functions to resolve replication problems by recruiting
repair proteins, activating checkpoints and promoting apoptosis. Cancers are characterized by genome
instability and have a greater need for functional DDR pathways. This provides opportunities for therapeutic
intervention, and in recent years, inhibitors have been developed targeting components of the DDR. The
overall goal of this proposal is to elucidate the mechanisms of genome maintenance that operate during DNA
replication. To address this broad goal, I propose three aims – 1) To determine the mechanisms by which the
single strand DNA binding protein, RPA, regulates the DDR protein, SMARCAL1 2) Discovery and functional
characterization of a novel alternative single strand DNA binding protein and 3) Mechanistic understanding of
how DNA repair proteins work in the context of chromatin structure. While aims 1 and 2 will be completed by
the end of my pre-doctoral studies, aim 3 represents the research direction I will adopt in my post-doctoral
work. To accomplish these aims, I will utilize new methods such as single molecule, genome wide and
proteomic approaches, as well as biochemical, molecular and genetic techniques. Completion of the proposed
aims will yield significant insights into novel genome maintenance pathways and will further our understanding
of the mechanisms underlying cancer biogenesis.

## Key facts

- **NIH application ID:** 9888359
- **Project number:** 5K00CA212435-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Kamakoti P. Bhat
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $92,233
- **Award type:** 5
- **Project period:** 2018-04-01 → 2020-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888359

## Citation

> US National Institutes of Health, RePORTER application 9888359, Molecular mechanisms of genome maintenance during DNA replication and repair (5K00CA212435-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9888359. Licensed CC0.

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