Journal article
Genome-wide screen reveals dependence of break induced replication on several distinct checkpoints
Nature communications, Vol.17(1), 494
2026
DOI: 10.1038/s41467-025-67182-w
PMCID: PMC12804954
PMID: 41398407
Abstract
Break-induced replication (BIR) is a primary homologous recombination pathway for repairing one-ended double-strand DNA breaks, including those arising from collapsed replication forks and eroded telomeres. BIR frequently leads to loss of heterozygosity, genetic mutations, and gross chromosomal rearrangements, all hallmarks of cancer. Here, we conducted a genome-wide screen that allowed us to identify and validate the involvement of 33 novel yeast genes in BIR. We report that, while DNA damage and spindle checkpoint machineries are both required to delay nuclear division and provide adequate time for BIR to complete, the spindle position checkpoint is required to coordinate between nuclear division and cytokinesis. Furthermore, we show that two nucleopore proteins play a sequential role during BIR: Nup84 acts before DNA synthesis, while Nup188 functions later to support repair completion. Given the conservation of BIR between yeast and humans and the role of BIR in cancer development, human homologs of the identified BIR proteins may represent promising targets for anti-cancer therapeutics.
Details
- Title: Subtitle
- Genome-wide screen reveals dependence of break induced replication on several distinct checkpoints
- Creators
- Liping Liu - The University of Texas Health Science Center at San AntonioRosemary S Lee - The University of Texas Health Science Center at San AntonioJerzy M Twarowski - University of IowaTimothy Emagbetere - The University of Texas Health Science Center at San AntonioJessie Thomas - The University of Texas Health Science Center at San AntonioJacob M Wells - The University of Texas Health Science Center at San AntonioGabriel J Seuferer - The University of Texas Health Science Center at San AntonioKirill Lobachev - Georgia Institute of TechnologyAnna Malkova - The University of Texas Health Science Center at San Antonio
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.17(1), 494
- DOI
- 10.1038/s41467-025-67182-w
- PMID
- 41398407
- PMCID
- PMC12804954
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Springer Nature
- Grant note
- R35GM127006 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Electronic publication date
- 12/15/2025
- Date published
- 2026
- Academic Unit
- Biology
- Record Identifier
- 9985090588102771
Metrics
3 Record Views