The homologous recombination component EEPD1 is required for genome stability in response to developmental stress of vertebrate embryogenesis

Changzoon Chun, Yuehan Wu, Suk-Hee Lee, Elizabeth A. Williamson, Brian L. Reinert, Aruna Shanker Jaiswal, Jac A. Nickoloff, Robert A. Hromas

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR), initiated by nuclease cleavage of branched structures at stalled forks. We previously reported that the 5′ nuclease EEPD1 is recruited to stressed replication forks, where it plays critical early roles in HR initiation by promoting fork cleavage and end resection. HR repair of stressed replication forks prevents their repair by non-homologous end-joining (NHEJ), which would cause genome instability. Rapid cell division during vertebrate embryonic development generates enormous pressure to maintain replication speed and accuracy. To determine the role of EEPD1 in maintaining replication fork integrity and genome stability during rapid cell division in embryonic development, we assessed the role of EEPD1 during zebrafish embryogenesis. We show here that when EEPD1 is depleted, zebrafish embryos fail to develop normally and have a marked increase in death rate. Zebrafish embryos depleted of EEPD1 are far more sensitive to replication stress caused by nucleotide depletion. We hypothesized that the HR defect with EEPD1 depletion would shift repair of stressed replication forks to unopposed NHEJ, causing chromosome abnormalities. Consistent with this, EEPD1 depletion results in nuclear defects including anaphase bridges and micronuclei in stressed zebrafish embryos, similar to BRCA1 deficiency. These results demonstrate that the newly characterized HR protein EEPD1 maintains genome stability during embryonic replication stress. These data also imply that the rapid cell cycle transit seen during embryonic development produces replication stress that requires HR to resolve.

Original languageEnglish (US)
Pages (from-to)957-962
Number of pages6
JournalCell Cycle
Volume15
Issue number7
DOIs
StatePublished - Apr 2 2016

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Genomic Instability
Homologous Recombination
Embryonic Development
Vertebrates
Zebrafish
Embryonic Structures
Cell Division
Recombinational DNA Repair
Anaphase
Chromosome Aberrations
Cell Cycle
Nucleotides
Pressure
Mortality
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

The homologous recombination component EEPD1 is required for genome stability in response to developmental stress of vertebrate embryogenesis. / Chun, Changzoon; Wu, Yuehan; Lee, Suk-Hee; Williamson, Elizabeth A.; Reinert, Brian L.; Jaiswal, Aruna Shanker; Nickoloff, Jac A.; Hromas, Robert A.

In: Cell Cycle, Vol. 15, No. 7, 02.04.2016, p. 957-962.

Research output: Contribution to journalArticle

Chun, C, Wu, Y, Lee, S-H, Williamson, EA, Reinert, BL, Jaiswal, AS, Nickoloff, JA & Hromas, RA 2016, 'The homologous recombination component EEPD1 is required for genome stability in response to developmental stress of vertebrate embryogenesis', Cell Cycle, vol. 15, no. 7, pp. 957-962. https://doi.org/10.1080/15384101.2016.1151585
Chun, Changzoon ; Wu, Yuehan ; Lee, Suk-Hee ; Williamson, Elizabeth A. ; Reinert, Brian L. ; Jaiswal, Aruna Shanker ; Nickoloff, Jac A. ; Hromas, Robert A. / The homologous recombination component EEPD1 is required for genome stability in response to developmental stress of vertebrate embryogenesis. In: Cell Cycle. 2016 ; Vol. 15, No. 7. pp. 957-962.
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