Downstream Transcription Promotes Human Recurrent CNV Associated AT-rich Sequence Mediated Genome Rearrangements in Yeast

Overview

Journal iScience

Publisher Cell Press

Date 2025 Jan 6

PMID 39758996

Authors

Feng-Yun Xie

Xiao-Guohui Zhang

Juan Chen

Xin Xu

Sen Li

Tian-Jin Xia

Lei-Ning Chen

Shen Yin

Xiang-Hong Ou

Jun-Yu Ma

Affiliations

Soon will be listed here.

Abstract

AT-rich sequence can cause structure variants such as translocations and its instability can be accelerated by replication stresses. When human 16p11.2 or 22q11.2 recurrent copy number variant (reCNV) associated AT-rich sequence was inserted upstream promoter in yeast genome, we found that downstream transcription could promote AT-rich forming cruciform structure and mediate gross genome rearrangements. When genes were flanked with direct repeats containing AT-rich sequence, copy number loss of these genes would be stimulated. Transcription-mediated AT-rich instability can be alleviated by disrupting or and exacerbated by disrupting . Deletion of homologous recombination-associated genes can not only increase AT-rich fragility but also alter the breakpoint positions. AT-rich stability was also affected by DNA topoisomerase poisons. Our results reveal that transcription can promote AT-rich-mediated genome rearrangement, which might be helpful for understanding the mechanism of reCNV formation in humans.

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