Abstract 2472: Defining the role of the XAB2 complex during homologous recombination

Abstract

Abstract Several factors associated with RNA processing are important for homologous recombination (HR), but the mechanistic links between these processes remain poorly understood. To this end, we have examined the function of the tetratricopeptide repeat factor XAB2 in HR, since this factor has a conserved function in RNA processing. We have found that XAB2 is important for chromosomal double strand break (DSB) repair via two pathways of HR that require end resection as an intermediate step, end resection of camptothecin (Cpt) induced DNA damage, and RAD51 recruitment to ionizing radiation induced foci (IRIF). Furthermore, XAB2 mediates CtIP hyperphosphorylation induced by Cpt and BRCA1 IRIF, as well as histone acetylation events linked to HR proficiency. The capacity for XAB2 to promote HR correlates with its ability to form a complex with ISY1 and PRP19, which show a similar influence as XAB2 on HR. Our recent efforts include examining other members of the XAB2 complex, as well as the transcription unit aberrations caused by loss of this complex, which may contribute to the defects in HR. Citation Format: David O. Onyango, Jeremy Stark. Defining the role of the XAB2 complex during homologous recombination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2472. doi:10.1158/1538-7445.AM2017-2472