RecQL4 interacts with MRN complex to regulate DNA damage response

Abstract

DNA double strand breaks (DSBs) are a major threat to cell viability and thus needs to be repaired timely and accurately by DNA repair pathways. RecQL4, a member of the RecQ helicase family, known to be involved in the initiation of DNA replication, is evident to play a critical role in DNA repair in response to DNA DSBs. RecQL4 is found to interact with Mre11-Rad50-Nbs1 (MRN) complex in response to DNA damage, which is one of the early and major sensors of DNA DSBs. In this paper, the interaction between RecQL4 and MRN complex is investigated by immunoprecipitation and immunostaining. It is confirmed that RecQL4 interacts directly with Mre11 among the components of this complex. It is further proved that it is the C-terminus of RecQL4 that is responsible for this interaction. Having proven that RecQL4 interacts with MRN complex, the role of RecQL4 in DNA repair is further questioned. It is found that RecQL4 is needed in Rad51 recruitment in response to DNA DSBs. Since mutations in the RecQL4 gene leads to the development of Rothmund-Thomson syndrome (RTS), this study will contribute to the understanding of maintenance of the genome integrity and DNA repair mechanisms.