First Author | Zhao F | Year | 2021 |
Journal | Nat Cell Biol | Volume | 23 |
Issue | 8 | Pages | 894-904 |
PubMed ID | 34354233 | Mgi Jnum | J:325306 |
Mgi Id | MGI:6860473 | Doi | 10.1038/s41556-021-00723-9 |
Citation | Zhao F, et al. (2021) ASTE1 promotes shieldin-complex-mediated DNA repair by attenuating end resection. Nat Cell Biol 23(8):894-904 |
abstractText | The shieldin complex functions as the downstream effector of 53BP1-RIF1 to promote DNA double-strand break end-joining by restricting end resection. The SHLD2 subunit binds to single-stranded DNA ends and blocks end resection through OB-fold domains. Besides blocking end resection, it is unclear how the shieldin complex processes SHLD2-bound single-stranded DNA and promotes non-homologous end-joining. Here, we identify a downstream effector of the shieldin complex, ASTE1, as a structure-specific DNA endonuclease that specifically cleaves single-stranded DNA and 3' overhang DNA. ASTE1 localizes to DNA damage sites in a shieldin-dependent manner. Loss of ASTE1 impairs non-homologous end-joining, leads to hyper-resection and causes defective immunoglobulin class switch recombination. ASTE1 deficiency also causes resistance to poly(ADP-ribose) polymerase inhibitors in BRCA1-deficient cells owing to restoration of homologous recombination. These findings suggest that ASTE1-mediated 3' single-stranded DNA end cleavage contributes to the control of DSB repair choice by 53BP1, RIF1 and shieldin. |