Homologous recombination conserves DNA sequence integrity throughout the cell cycle in embryonic stem cells

Lourdes Serrano, Li Liang, Yiming Chang, Li Deng, Christopher Maulion, Son Nguyen, Jay A. Tischfield

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The maintenance of genomic integrity is crucial to embryonic stem cells (ESC) considering the potential for propagating undesirable mutations to the resulting somatic and germ cell lineages. Indeed, mouse ESC (mESC) exhibit a significantly lower mutation frequency compared to differentiated cells. This could be due to more effective elimination of genetically damaged cells via apoptosis, or especially robust, sequence-conserving DNA damage repair mechanisms such as homologous recombination (HR). We used fluorescence microscopy and 3-dimensional image analysis to compare mESC and differentiated cells, with regard to HR-mediated repair of spontaneous and X-ray-induced double-strand breaks (DSBs). Microscopic analysis of repair foci, flow cytometry, and functional assays of the major DSB repair pathways indicate that HR is greater in mESC compared to fibroblasts. Strikingly, HR appears to be the predominant pathway choice to repair induced or spontaneous DNA damage throughout the ESC cycle in contrast to fibroblasts, where it is restricted to replicated chromatin. This suggests that alternative templates, such as homologous chromosomes, are more frequently used to repair DSB in ESC. Relatively frequent HR utilizing homolog chromosome sequences preserves genome integrity in ESC and has distinctive and important genetic consequences to subsequent somatic and germ cell lineages.

Original languageEnglish (US)
Pages (from-to)363-374
Number of pages12
JournalStem Cells and Development
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2011

All Science Journal Classification (ASJC) codes

  • Hematology
  • Cell Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Homologous recombination conserves DNA sequence integrity throughout the cell cycle in embryonic stem cells'. Together they form a unique fingerprint.

  • Cite this