Role of Γ-H2AX in DNA damage response

Abstract

Little is known about the molecular mechanism of γ-H2AX in DNA damage response in mammalian embryos when compared to the somatic cells. An integrative review of the literature on the molecular mechanism of γ-H2AX in DNA damage response in somatic cells and in mammalian embryos was performed. The objective of the study is to summarize and synthesize the published databased literature over the last 10 years on molecular mechanism of γ-H2AX in mouse pre-implantation embryos and somatic cells using the key words--"γ-H2AX", "DNA damage", "somatic cells", "mouse embryo". An initial medline search was performed using our inclusion and exclusion criteria and then expanded by snowballing. The articles were compiled in the form of a Review Matrix. The knowledge gap was investigated and the conceptual model was formulated to hypothesize the sequence of DNA damage responses occurring during the time of early mouse embryogenesis. Major themes drawn from the studies are-1). Periodic appearance and disappearance of γ-H2AX in early mouse pre-implantation embryos, 2) Development of γ-H2AX foci in the pronuclei without imposing any replicative stress on the mouse embryo, 3) Occurrence of γ-H2AX in the S-phase of somatic cells under replicative stress and normal embryos, 4) Prevalence of prominent γ-H2AX signal in male pronuclei compared to the female pronuclei during mouse embryogenesis. The study will also show scopes of future research to explore the arena in clinical context.