The RAD51 S181P mutation shortens lifespan of female mice

Mutat Res. 2024 Jul-Dec:829:111878. doi: 10.1016/j.mrfmmm.2024.111878. Epub 2024 Aug 2.

Abstract

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.

Keywords: Double strand break repair; Homologous recombination; Lifespan; Replication fork maintenance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics
  • DNA Replication
  • Female
  • Longevity* / genetics
  • Lymphoma / genetics
  • Lymphoma / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Rad51 Recombinase* / genetics
  • Rad51 Recombinase* / metabolism

Substances

  • Rad51 Recombinase
  • Rad51 protein, mouse