Roles of Brain and Reproductive Organ-Expressed Protein in DNA Damage Recognition and Repair Responds of Mouse Embryonic Stem Cells
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AbstractPluripotent mouse embryonic stem cells (mESCs) can undergo self-renewal and long-term proliferation, together with the ability to differentiate into various cell types. External factors, such as gamma irradiation, can induce DNA double-strand breaks. Inability to properly repair the DNA lesion will lead to genomic instability and mutations. Consequently, the build-up of mutation in mESCs may lead to metastasis and developmental defect. Hence, it is essential that the genetic integrity is maintained to prevent accumulation of mutation in mESCs. Brain and Reproductive Organ-Expressed protein (BRE), also known as BRCC45, is a component of the BRCA1-A complex. It is involved in the recognition of DNA double strand break and assists in the initiation of DNA repair response. We have previously demonstrated that knocking-out BRE expression in mouse tail fibroblast impaired BRCA1-A complex recruitment which subsequently leads to premature cellular senescence upon gamma irradiation treatment. However, mESCs can undergo self-renewal and long term proliferation. Moreover, mESCs have a significantly shortened cell cycle compared with fibroblasts, with defected cell cycle checkpoint, than other normal differentiated cells. Distinctive types of DNA damage response and DNA repair mechanism might be found in mESCs. In order to study the role of BRE in mESCs, we have generated BRE knockout (BRE-/-) mESCs from blastocyst of BRE-/- mice. Our results show that γ-H2AX foci, a DNA damage marker, expression is higher in BRE-/- mESCs than in WT mESCs. We will in future investigate and elucidate how the DNA repair is affected in BRE-/- mESCs and would the buildup of mutations affect embryonic development.
All Author(s) ListCHUNG Cheuk Yiu Tenny, LEE Ka Ho Kenneth, LO Hau Yi Paulisally
Name of Conference2017 ISSCR Annual Meeting
Start Date of Conference14/06/2017
End Date of Conference17/06/2017
Place of ConferenceBoston Convention and Exhibition Center (BCEC)
Country/Region of ConferenceUnited States of America
LanguagesEnglish-United States

Last updated on 2018-18-01 at 08:32