The RAD51 S181P mutation shortens lifespan of female mice

Sherry G Dodds; Gene Hubbard; Yong Jun Choi; Kyungjae Myung; Gene Elliot; Lisa Garrett; Tae Moon Kim; Paul Hasty

doi:10.1016/j.mrfmmm.2024.111878

The RAD51 S181P mutation shortens lifespan of female mice

Mutat Res. 2024 Aug 2:829:111878. doi: 10.1016/j.mrfmmm.2024.111878. Online ahead of print.

Authors

Sherry G Dodds¹, Gene Hubbard², Yong Jun Choi³, Kyungjae Myung⁴, Gene Elliot⁵, Lisa Garrett⁵, Tae Moon Kim⁶, Paul Hasty⁷

Affiliations

¹ Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, Texas, USA.
² 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.
³ Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea.
⁴ Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea; Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
⁵ Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁶ Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea. Electronic address: bio92xa72@gmail.com.
⁷ Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, Texas, USA; Mays Cancer Center, University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, Texas, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, USA. Electronic address: hastyhsc@gmail.com.

PMID: 39151334
DOI: 10.1016/j.mrfmmm.2024.111878

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.