# Genome-Wide Single-Molecule Analysis of Human Replication Kinetics

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $488,129

## Abstract

PROJECT SUMMARY
The timing of DNA replication is a critical parameter of cellular growth. It correlates with
patterns of transcriptional regulation, chromatin modification, chromosome structure and
genome evolution. Furthermore, replication timing changes as cells differentiate, and
disruption of replication timing correlates with genome instability, suggesting an intimate
relation between replication timing and other important aspects of chromosome metabolism. A
major impediment to understand the regulation of replication timing in the human genome has
been the lack of robust assays for identifying the location and firing times of human replication
origins. Current approaches suffer from low signal-to-noise ratios and poor concordance
between independent laboratories. Moreover, ensemble techniques are unable to probe the
coordination of origin firing, a subject significant interest in the field, because it has been
proposed as a key factor in replication timing and efficiency. We propose to apply two new
high-throughput single-molecule approaches that we have developed—Optical Replication
Mapping and SMRT Repli-seq—to map replication origins and replication fork progression
across the human genome. We will use replication profiles that we obtain to develop
hypotheses about fundamental aspects of genome biology, such as such as how replication and
transcription are coordinated, if the location of replication termination sites are regulated and
how forks navigate difficult-to-replicate sequences. Successful completion of this work will
elucidate the regulation of replication timing across the human genome, allow for the
characterization of the sequence and epigenetic determinants for origin function, and provide
robust origin maps and replication profiles for others to use. Moreover, dissemination of this
technology will change the questions that biologists are able to ask about the regulation of DNA
replication timing and its repercussions in diverse fields, such as development, chromatin
biology, and epigenetics.

## Key facts

- **NIH application ID:** 10221728
- **Project number:** 5R01GM125872-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** NICHOLAS R RHIND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $488,129
- **Award type:** 5
- **Project period:** 2018-08-23 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221728

## Citation

> US National Institutes of Health, RePORTER application 10221728, Genome-Wide Single-Molecule Analysis of Human Replication Kinetics (5R01GM125872-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10221728. Licensed CC0.

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