Female-biased embryonic death from inflammation induced by genomic instability.

ABSTRACT: Genomic instability can trigger cellular responses that include checkpoint activation, senescence and inflammation^1,2. Although genomic instability has been extensively studied in cell culture and cancer paradigms, little is known about its effect during embryonic development, a period of rapid cellular proliferation. Here we report that mutations in the heterohexameric minichromosome maintenance complex-the DNA replicative helicase comprising MCM2 to MCM7^3,4-that cause genomic instability render female mouse embryos markedly more susceptible than males to embryonic lethality. This bias was not attributable to X chromosome-inactivation defects, differential replication licensing or X versus Y chromosome size, but rather to 'maleness'-XX embryos could be rescued by tra

SUBMITTER: McNairn AJ 

PROVIDER: S-EPMC6497049 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature