Last update 01 Nov 2024

NABP2

Last update 01 Nov 2024

Basic Info

Synonyms

hSSB1, MGC2731, NABP2

+ [10]

Introduction

Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint (PubMed:25249620). In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA, in particular to polypyrimidines. The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways.

Drugs associated with NABP2

DKLS02

Target

NABP2

Mechanism

NABP2 inhibitors

Active Org.

Princess Alexandra Hospital [+1]

Originator Org.

Queensland University of Technology [+1]

Active Indication

Non-Small Cell Lung Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NABP2

100 Translational Medicine associated with NABP2

0 Patents (Medical) associated with NABP2

Literatures (Medical) associated with NABP2

01 Sep 2024·iScience

Redox-dependent condensation and cytoplasmic granulation by human ssDNA-binding protein-1 delineate roles in oxidative stress response

Article

Author: Jezsó, Bálint ; Szakács, Gergely ; Harami-Papp, Hajnalka ; Kucsma, Nóra ; Kovács, Zoltán J ; Harami, Gábor M ; Pálinkás, János ; Mahmudova, Lamiya ; Tóth, Szilárd ; Kovács, Mihály ; Harami, Gábor M. ; Tárnok, Krisztián ; Kovács, Zoltán J. ; Hegedüs, József

Human single-stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) plays central roles in DNA repair. Here, we show that purified hSSB1 undergoes redox-dependent liquid-liquid phase separation (LLPS) in the presence of single-stranded DNA or RNA, features that are distinct from those of LLPS by bacterial SSB. hSSB1 nucleoprotein droplets form under physiological ionic conditions in response to treatment modeling cellular oxidative stress. hSSB1's intrinsically disordered region is indispensable for LLPS, whereas all three cysteine residues of the oligonucleotide/oligosaccharide-binding fold are necessary to maintain redox-sensitive droplet formation. Proteins interacting with hSSB1 show selective enrichment inside hSSB1 droplets, suggesting tight content control and recruitment functions for the condensates. While these features appear instrumental for genome repair, we detected cytoplasmic hSSB1 condensates in various cell lines colocalizing with stress granules upon oxidative stress, implying extranuclear function in cellular stress response. Our results suggest condensation-linked roles for hSSB1, linking genome repair and cytoplasmic defense.

01 Apr 2024·Protein Science

DNA‐dependent phase separation by human SSB2 (NABP1/OBFC2A) protein points to adaptations to eukaryotic genome repair processes

Article

Author: Harami-Papp, Hajnalka ; Khamisi, Lana ; Harami, Gábor M ; Kovács, Zoltán J ; Hegedüs, József ; Kovács, Mihály ; Mahmudova, Lamiya ; Kuljanishvili, Natalie ; Szakács, Gergely ; Pálinkás, János

AbstractSingle‐stranded DNA binding proteins (SSBs) are ubiquitous across all domains of life and play essential roles via stabilizing and protecting single‐stranded (ss) DNA as well as organizing multiprotein complexes during DNA replication, recombination, and repair. Two mammalian SSB paralogs (hSSB1 and hSSB2 in humans) were recently identified and shown to be involved in various genome maintenance processes. Following our recent discovery of the liquid–liquid phase separation (LLPS) propensity of Escherichia coli (Ec) SSB, here we show that hSSB2 also forms LLPS condensates under physiologically relevant ionic conditions. Similar to that seen for EcSSB, we demonstrate the essential contribution of hSSB2's C‐terminal intrinsically disordered region (IDR) to condensate formation, and the selective enrichment of various genome metabolic proteins in hSSB2 condensates. However, in contrast to EcSSB‐driven LLPS that is inhibited by ssDNA binding, hSSB2 phase separation requires single‐stranded nucleic acid binding, and is especially facilitated by ssDNA. Our results reveal an evolutionarily conserved role for SSB‐mediated LLPS in the spatiotemporal organization of genome maintenance complexes. At the same time, differential LLPS features of EcSSB and hSSB2 point to functional adaptations to prokaryotic versus eukaryotic genome metabolic contexts.

01 Dec 2023·Cell Reports

The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks

Article

Author: Sedova, Katerina ; Haluza, Vojtech ; Gullerova, Monika ; Sebesta, Marek ; Alagia, Adele ; Liu, Zhichao ; Stefl, Richard ; Long, Qilin

Double-strand breaks (DSBs) are the most severe type of DNA damage. Previously, we demonstrated that RNA polymerase II (RNAPII) phosphorylated at the tyrosine 1 (Y1P) residue of its C-terminal domain (CTD) generates RNAs at DSBs. However, the regulation of transcription at DSBs remains enigmatic. Here, we show that the damage-activated tyrosine kinase c-Abl phosphorylates hSSB1, enabling its interaction with Y1P RNAPII at DSBs. Furthermore, the trimeric SOSS1 complex, consisting of hSSB1, INTS3, and c9orf80, binds to Y1P RNAPII in response to DNA damage in an R-loop-dependent manner. Specifically, hSSB1, as a part of the trimeric SOSS1 complex, exhibits a strong affinity for R-loops, even in the presence of replication protein A (RPA). Our in vitro and in vivo data reveal that the SOSS1 complex and RNAPII form dynamic liquid-like repair compartments at DSBs. Depletion of the SOSS1 complex impairs DNA repair, underscoring its biological role in the R-loop-dependent DNA damage response.

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NABP2

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