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Related Experiment Video

Updated: Apr 28, 2026

Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion

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Published on: September 13, 2024

Break-induced replication is a source of mutation clusters underlying kataegis.

Cynthia J Sakofsky¹, Steven A Roberts², Ewa Malc³

¹Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324, USA; Department of Biology, School of Science, IUPUI, Indianapolis, IN 46202-5132, USA.

|June 3, 2014

Summary

Double-strand break-induced replication (BIR) creates mutation clusters in yeast, similar to cancer kataegis. These clusters arise from DNA damage in single-stranded DNA during BIR replication intermediates.

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Area of Science:

Genetics
Molecular Biology
Cancer Research

Background:

Mutation clusters drive rapid evolutionary and carcinogenic changes.
Previous studies linked mutation clusters to DNA damage in single-stranded DNA (ssDNA) at resected double-strand breaks and stalled replication forks.

Purpose of the Study:

To investigate double-strand break (DSB)-induced break-induced replication (BIR) as a novel source of mutation clusters.
To characterize the nature and mechanisms of mutation clusters formed during BIR.

Main Methods:

Induction of BIR in wild-type yeast cells with alkylating damage.
Analysis of mutation patterns, including base specificity, strand coordination, and bias.
Characterization of associated DNA breakage and rearrangements.

Main Results:

BIR generated mutation clusters in nearly half of yeast cells.
Mutations were concentrated along the DNA synthesis track.
BIR-associated mutation clusters showed features consistent with damage in persistent ssDNA within unconventional replication intermediates.
These clusters were linked to additional breakage and rearrangements.

Conclusions:

DSB-induced BIR is a significant source of mutation clusters.
The findings suggest BIR replication intermediates are a major source of mutation clusters across species.
This mechanism may contribute to kataegis-like events observed in cancer genomes.