DNA repair regulates more than you think

Abstract

Oxidative damage to DNA and its repair are ongoing processes in all cells. The key means to repair is the base excision repair pathway; the key enzyme is AP endonuclease 1 (Apex1). Knockout of Apex1 in mice is embryonically lethal and no null cells have been cultured. We study Apex1 in zebrafish, because zebrafish provide an excellent system for following the earliest stages of embryological development. Complete knockdown of Apex1 following fertilization leads to embryonic death at 3.5 hours post fertilization, just as differentiation is about to begin. Partial knockdown results in defective brain and heart development. The embryos will die within 7 days when a functional heart is required for development to progress. In this study, we explore the initial events that occur upon knockdown of Apex1. We present data showing that loss of Apex1 protein after knockdown begins 2.5 hours later. The first detected changes in transcription are increases in histone H2B, while transcription of other histones does not change relative to controls. The important transcription factor Creb1 as well as DNA repair polymerase