hSSB1 associates with and promotes stability of the BLM helicase

BMC Molecular Biology

Research Article

Nicholas W. Ashton¹  Emma Bolderson¹  Nicolas Paquet¹  Laura V. Croft¹  Derek J. Richard¹  Kenneth J. O’Byrne² 

[1] School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, 37 Kent Street, 4102, Woolloongabba, QLD, Australia;School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, 37 Kent Street, 4102, Woolloongabba, QLD, Australia;Princess Alexandra Hospital, 199 Ipswich Road, 4102, Woolloongabba, QLD, Australia;

关键词: HSSB1;    BLM;    DNA damage;    DNA repair;    Double strand breaks;    Replication stress;   

DOI  :  10.1186/s12867-017-0090-3

 received in 2016-09-29, accepted in 2017-05-05,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMaintenance of genome stability is critical in human cells. Mutations in or loss of genome stability pathways can lead to a number of pathologies including cancer. hSSB1 is a critical DNA repair protein functioning in the repair and signalling of stalled DNA replication forks, double strand DNA breaks and oxidised DNA lesions. The BLM helicase is central to the repair of both collapsed DNA replication forks and double strand DNA breaks by homologous recombination.ResultsIn this study, we demonstrate that hSSB1 and BLM helicase form a complex in cells and the interaction is altered in response to ionising radiation (IR). BLM and hSSB1 also co-localised at nuclear foci following IR-induced double strand breaks and stalled replication forks. We show that hSSB1 depleted cells contain less BLM protein and that this deficiency is due to proteasome mediated degradation of BLM. Consequently, there is a defect in recruitment of BLM to chromatin in response to ionising radiation-induced DSBs and to hydroxyurea-induced stalled and collapsed replication forks.ConclusionsOur data highlights that BLM helicase and hSSB1 function in a dynamic complex in cells and that this complex is likely required for BLM protein stability and function.

【 授权许可】

CC BY   
© The Author(s) 2017