Language
English
Publication Date
7-1-2026
Journal
Nature Structural & Molecular Biology
DOI
10.1038/s41594-026-01832-5
PMID
42443617
PMCID
PMC13456139
PubMedCentral® Posted Date
8-11-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Break-induced DNA replication (BIR) is a highly mutagenic recombination pathway used by eukaryotic cells to repair single-ended DNA breaks, mediate mitotic DNA synthesis and promote telomerase-independent telomere maintenance in certain cancers. Leading-strand synthesis in BIR is mediated by a migrating D-loop driven by DNA polymerase δ and Pif1 helicase but the mechanism of second-strand synthesis has remained poorly understood. Here we demonstrate that in yeast cells lacking Cdc13-Stn1-Ten1 (CST complex), the early steps of BIR including 5' strand resection, D-loop formation and first-strand synthesis proceed normally. However, second-strand synthesis is impaired, implicating CST in this critical BIR step. The function of CST in BIR is conserved in human cells. Using biochemical reconstitution with DNA substrates mimicking BIR intermediates, we demonstrate that yeast CST promotes second-strand synthesis by enhancing DNA polymerase α-primase activity. Our findings provide mechanistic insight into how BIR supports long-tract DNA synthesis independently of the S-phase replisome.
Keywords
DNA Replication, Saccharomyces cerevisiae Proteins, Saccharomyces cerevisiae, DNA Polymerase I, Cell Cycle Proteins, Telomere-Binding Proteins, DNA Helicases, DNA Primase, Humans, Chromosomal Proteins, Non-Histone, DNA Polymerase III
Published Open-Access
yes
Recommended Citation
Thakre, Pilendra; Wang, Jeff; Liu, Liping; et al., "Cst Complex Promotes Second-Strand Synthesis in Break-Induced Replication" (2026). Faculty, Staff and Students Publications. 8099.
https://digitalcommons.library.tmc.edu/baylor_docs/8099