ANKHD1 is an S phase protein required for histone synthesis and DNA repair in multiple myeloma cells

Abstract

ANKHD1 is highly expressed in various cancers such as leukemia and multiple myeloma. Silencing of ANKHD1 expression leads to decreased cell proliferation and accumulation of cells at the S phase. In this study we found ANKHD1 expression to be higher at the S phase, suggesting it to be an S phase protein. We observed that ANKHD1 interacts with histone promoter regions and its inhibition downregulates expression of all core histones, implying a role in histone synthesis. Since histone synthesis occurs in parallel with DNA replication at S phase, we evaluated PCNA (Proliferating Cell Nuclear Antigen) expression, a protein involved in DNA replication and repair. PCNA expression was found to be significantly decreased in ANKHD1 silenced cells. We further observed accumulation γH2AX, a marker for DNA double stranded breaks and an early sign of DNA damage induced by replication stress, upon ANKHD1 silencing. The expressions of several genes implicated in DNA repair were also modulated in ANKHD1 silenced cells, confirming the role of ANKHD1 in DNA repair. Based on this study we speculate that ANKHD1 is an S phase protein required for histone synthesis and DNA repair. These results however, are preliminary and require thorough investigation.

Keywords: Ankyrin repeat and KH domain-containing 1; DNA damage; Histones; Myeloma; Proliferating cell nuclear antigen; S phase.