Abstract 5139: MOF cooperates with DNA polymerase eta to repair intrastrand break induced by crosslinking agents

Abstract

Abstract The human MOF gene encodes a protein that specifically acetylates histone H4 at lysine 16 (H4K16ac). Reduced levels of H4K16ac correlate with a defective DNA damage response (DDR) and double-strand break (DSB) repair post ionizing radiation exposure. MOF overexpression increases cell survival to intrastrand crosslink inducing agents like cisplatin. DNA polymerase eta (Pol H), the product of the xeroderma pigmentosum variant (XPV) gene and a Y-family DNA polymerase, plays a pivotal role in translesion DNA synthesis and was found to interact with MOF. Its interaction with MOF increases in a dose dependent manner after exposure to intrastrand DNA damage induced by cisplatin. Pol H colocalized with phosphorylated MOF and γ-H2AX foci in cisplatin treated cells. Overexpression of MOF enhances recruitment of Pol H to laser induced DNA damage. This correlated with monoubiquitination of PCNA which has been shown to facilitate the switch between the replicative DNA polymerase with the low-fidelity polymerase eta to bypass UV or cisplatin-induced DNA lesions during replication. MOF was found to interact with PCNA and regulating the ubiquitination of PCNA thereby facilitating Pol H recruitment to DNA damage sites. Note: This abstract was not presented at the meeting. Citation Format: Mayank Singh, Arun Gupta, Komal Komal, Tej K. Pandita. MOF cooperates with DNA polymerase eta to repair intrastrand break induced by crosslinking agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5139. doi:10.1158/1538-7445.AM2014-5139