近日，德国癌症研究中心Duncan T. Odom等研究人员，合作实现急性和慢性DNA诱变与修复的单次有丝分裂剖析。这一研究成果于2024年4月16日在线发表在国际学术期刊《自然—遗传学》上。

据悉，人们对慢性突变过程和点状DNA损伤爆发，如何推动癌症基因组演化还知之甚少。

附：英文原文

Title: Single-mitosis dissection of acute and chronic DNA mutagenesis and repair

Author: Ginno, Paul Adrian, Borgers, Helena, Ernst, Christina, Schneider, Anja, Behm, Mikaela, Aitken, Sarah J., Taylor, Martin S., Odom, Duncan T.

Issue&Volume: 2024-04-16

Abstract: How chronic mutational processes and punctuated bursts of DNA damage drive evolution of the cancer genome is poorly understood. Here, we demonstrate a strategy to disentangle and quantify distinct mechanisms underlying genome evolution in single cells, during single mitoses and at single-strand resolution. To distinguish between chronic (reactive oxygen species (ROS)) and acute (ultraviolet light (UV)) mutagenesis, we microfluidically separate pairs of sister cells from the first mitosis following burst UV damage. Strikingly, UV mutations manifest as sister-specific events, revealing mirror-image mutation phasing genome-wide. In contrast, ROS mutagenesis in transcribed regions is reduced strand agnostically. Successive rounds of genome replication over persisting UV damage drives multiallelic variation at CC dinucleotides. Finally, we show that mutation phasing can be resolved to single strands across the entire genome of liver tumors from F1 mice. This strategy can be broadly used to distinguish the contributions of overlapping cancer relevant mutational processes.

DOI: 10.1038/s41588-024-01712-y

Source: https://www.nature.com/articles/s41588-024-01712-y