Ultrasensitive tumour‐agnostic non‐invasive detection of colorectal cancer recurrence using ctDNA methylation

Xiao, Yu; Wang, Xiaodong; Weng, Hong; Ding, Zhao; Qian, Kaiyu; Jin, Wan; Lu, Sen; Ju, Lingao; He, Zhong; Wang, Gang; Xie, Xiaoyu; Li, Dongmei; Zhang, Fan; Wu, Kai; Li, Sheng; Guo, Huanhuan; Qian, Guofeng; Jiang, Wei; Leng, Yunji; Zhao, Jingjing; Cao, Xinyue; Peng, Min‐Sheng; Jiang, Congqing; Li, Li; Zhang, Yi; Wang, Xinghuan

doi:10.1002/ctm2.1015

Cited by 1 publication

(1 citation statement)

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“…25 ng of genomic DNA was subjected to bisulfite conversion using a commercial kit (Zymo Research, #D5005). The converted product was 3’ tailed by dATP with terminal deoxynucleotide transferase (Enzymatics, #P7070L) in the presence of a tail-controlling adaptor, as described for the Tequila 7 N bisulfite capture sequencing assay 121 , and ligated to the adaptor with E. coli DNA ligase (Takara, #2161). The ligated product was amplified with a G-quadruplex-specific common primer (NGS-1290, 5’- GGAGGGGAGGGGAGAGGGG -3’) and an adaptor-specific common primer for 12 cycles with Phusion U (Thermo Fisher, #F555L).…”

Section: Methodsmentioning

confidence: 99%

A universal molecular mechanism driving aging

Jin,

Zheng,

Xiao

et al. 2024

Preprint

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How cell replication ultimately results in aging and the Hayflick limit are not fully understood. Here we show that clock-like accumulation of DNA G-quadruplexes (G4s) throughout cell replication drives conserved aging mechanisms. G4 stimulates transcription-replication interactions to delay genome replication and impairs DNA re-methylation and histone modification recovery, leading to loss of heterochromatin. This creates a more permissive local environment for G4 formation in subsequent generations. As a result, G4s gradually accumulate on promoters throughout mitosis, driving clock-like DNA hypomethylation and chromatin opening. In patients andin vitromodels, loss-of-function mutations in the G4-resolving enzymes WRN, BLM and ERCC8 accelerate the erosion of the epigenomic landscape around G4. G4-driven epigenomic aging is strongly correlated with biological age and is conserved in yeast, nematodes, insects, fish, rodents, and humans. Our results revealed a universal molecular mechanism of aging and provided mechanistic insight into how G-quadruplex processor mutations drive premature aging.

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Section: Methodsmentioning

confidence: 99%