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Last update 08 May 2025

ASTE1

Last update 08 May 2025

Basic Info

Synonyms

ASTE1, asteroid homolog 1, HT001

+ [1]

Introduction

Structure-specific DNA endonuclease that specifically cleaves single-stranded DNA and 3' overhang DNA. Contributes to the control of DNA double-strand break repair choice by antagonizing BRCA1-dependent homologous recombination (HR) and promoting non-homologous end-joining (NHEJ). Recruited to the single-stranded DNA ends by SHLD2 and cleaves the 3' exposed DNA ends, therefore inhibiting DNA end resection (necessary for HR) and promoting DNA end protection (necessary for NHEJ).

Drugs associated with ASTE1

FMPV-3

Target

ASTE1 x TAF1B x TGFBR2

Mechanism

ASTE1 modulators [+2]

Active Org.

Hubro Therapeutics AS

Originator Org.

Hubro Therapeutics AS

Active Indication

Hereditary Nonpolyposis Colorectal Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

FMPV-2

Target

ASTE1

Mechanism

ASTE1 modulators [+1]

Active Org.

Hubro Therapeutics AS

Originator Org.

Hubro Therapeutics AS

Active Indication

Endometrial Carcinoma

Inactive Indication

Colorectal Cancer

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ASTE1

100 Translational Medicine associated with ASTE1

0 Patents (Medical) associated with ASTE1

Literatures (Medical) associated with ASTE1

01 Aug 2021·Nature Cell Biology

ASTE1 promotes shieldin-complex-mediated DNA repair by attenuating end resection

Article

Author: Zhou, Qin ; Liu, Yilun ; Guo, Guijie ; Hu, Qi ; Kim, Wootae ; Gao, Huanyao ; Gao, Ming ; Zhang, Yong ; Zhang, Chao ; Yuan, Jian ; Luo, Kuntian ; Tu, Xinyi ; Deng, Min ; Chen, Shih-Hsun ; Yin, Ping ; Liu, Chao ; Lou, Zhenkun ; Qin, Sisi ; Qin, Bo ; Kloeber, Jake A ; Zhao, Fei ; Nowsheen, Somaira ; Chen, Yuping ; Huang, Jinzhou

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.

01 Aug 2021·Nature Cell Biology

ASTE1 cutting to block DNA end resection

Article

Author: He, Yizhou Joseph ; Chowdhury, Dipanjan

Cells rely on two main pathways to repair DNA lesions, homologous recombination and non-homologous end-joining, and how they decide to use one machinery over the other is not clear.A recent study identifies ASTE1 as a regulator controlling pathway choice.

01 Sep 2020·Clinical Cancer Research

A Frameshift Peptide Neoantigen-Based Vaccine for Mismatch Repair-Deficient Cancers: A Phase I/IIa Clinical Trial

Article

Author: Al-Batran, Salah-Eddin ; Pauligk, Claudia ; Reuschenbach, Miriam ; Kloor, Matthias ; Rafiyan, Mohammad-Reza ; Karbach, Julia ; Jäger, Elke ; Tariverdian, Mirjam ; von Knebel Doeberitz, Magnus

AbstractPurpose:DNA mismatch repair (MMR) deficiency is a hallmark of Lynch syndrome, the most common inherited cancer syndrome. MMR-deficient cancer cells accumulate numerous insertion/deletion mutations at microsatellites. Mutations of coding microsatellites (cMS) lead to the generation of immunogenic frameshift peptide (FSP) neoantigens. As the evolution of MMR-deficient cancers is triggered by mutations inactivating defined cMS-containing tumor suppressor genes, distinct FSP neoantigens are shared by most MMR-deficient cancers. To evaluate safety and immunogenicity of an FSP-based vaccine, we performed a clinical phase I/IIa trial (Micoryx).Patients and Methods:The trial comprised three cycles of four subcutaneous vaccinations (FSP neoantigens derived from mutant AIM2, HT001, TAF1B genes) mixed with Montanide ISA-51 VG over 6 months. Inclusion criteria were history of MMR-deficient colorectal cancer (UICC stage III or IV) and completion of chemotherapy. Phase I evaluated safety and toxicity as primary endpoint (six patients), phase IIa addressed cellular and humoral immune responses (16 patients).Results:Vaccine-induced humoral and cellular immune responses were observed in all patients vaccinated per protocol. Three patients developed grade 2 local injection site reactions. No vaccination-induced severe adverse events occurred. One heavily pretreated patient with bulky metastases showed stable disease and stable CEA levels over 7 months.Conclusions:FSP neoantigen vaccination is systemically well tolerated and consistently induces humoral and cellular immune responses, thus representing a promising novel approach for treatment and even prevention of MMR-deficient cancer.

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ASTE1

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