Authors
Pilendra Thakre, Jeff Wang, Liping Liu, Sameer Shah, Zhenxin Yan, Nhung Pham, Meng-Chia Tsai, Yuqin Zhao, Cody M Rogers, Zhitong Feng, Hengyao Niu, Youngho Kwon, Xiaohua Wu, Anna Malkova, Patrick Sung, Grzegorz Ira
Published in
Nature structural & molecular biology. Jul 13, 2026. Epub Jul 13, 2026.
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.
PMID:
42443617
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.
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