Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, Texas, USA.
Department of Pathology, University of Texas Health San Antonio, San Antonio, Texas, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, USA.
Mutat Res. 2024 Jul-Dec;829:111878. doi: 10.1016/j.mrfmmm.2024.111878. Epub 2024 Aug 2.
RAD51 is critical to the homologous recombination (HR) pathway that repairs DNA double strand breaks (DSBs) and protects replication forks (RFs). Previously, we showed that the S181P (SP) mutation in RAD51 causes defective RF maintenance but is proficient for DSB repair. Here we report that SP/SP female mice exhibit a shortened lifespan compared to +/+ females but not males. Histological analysis found that most mice in this study died from lymphoma, independent of genotype and sex. We propose that a potential cause for shortened lifespan in SP/SP females is due to the RF defect.
RAD51 对于同源重组 (HR) 途径至关重要，该途径可修复 DNA 双链断裂 (DSBs) 并保护复制叉 (RFs)。 之前，我们表明 RAD51 的 S181P (SP) 突变导致 RF 维持缺陷，但 DSB 修复效率正常。 在这里，我们报告说 SP/SP 雌性小鼠的寿命比 +/+ 雌性小鼠短，但与雄性小鼠没有区别。 组织学分析发现，本研究中的大多数小鼠死于淋巴瘤，与基因型和性别无关。 我们提出，SP/SP 雌性小鼠寿命缩短的一个潜在原因是 RF 缺陷。
