SLX4 and SLX4IP TAP-MS - SLX4IP acts with SLX4 and XPF-ERCC1 to promote interstrand crosslink repair

ABSTRACT: Interstrand crosslinks (ICLs) are highly toxic DNA lesions, which are repaired via a complex process that requires the coordination of several DNA repair pathways. Defects in ICL repair result in Fanconi anemia (FA), which is diagnosed with bone marrow failure, development abnormalities and high incidence of malignancies. SLX4, which is also known as FANCP, acts as a scaffold protein in coordinating multi-endonucleases that function in unhooking ICLs, resolving homologous recombination intermediates, and perhaps also removing unhooked ICLs. To reveal the underlying mechanism for the involvement of SLX4IP in ICL repair, we tagged SFB to the C terminus of SLX4IP and performed tandem affinity purification and mass spectrometry analysis as outlined above. We found SLX4 and XPF-ERCC1 at the top of the list of SLX4IP-binding proteins. We also identified some other potential SLX4IP interacting proteins, such as PASK, AJUBA, LRP4 and TRIM26, but none of them has been previously indicated to participate in DNA repair. SLX4 and XPF-ERCC1 are the major SLX4IP-interacting proteins, with or without MMC treatment. SLX4 has been shown to coordinate with XPF-ERCC1 and participate in the unhooking of ICLs during the repair process. The binding of SLX4IP to both SLX4 and XPF-ERCC1 intrigued us to further investigate whether SLX4IP plays a role in regulating SLX4-XPF-ERCC1 interaction.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Zhen Chen  

LAB HEAD: Junjie Chen

PROVIDER: PXD012521 | Pride | 2019-09-13

REPOSITORIES: Pride