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nabp2

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Official Full Name
nucleic acid binding protein 2
Synonyms
SSB1; hSSB1; OBFC2B; SOSS-B1

NABP2 encodes a protein SOSS complex subunit B1, which is a single-stranded DNA (ssDNA)-binding proteins that are ubiquitous and essential for a variety of DNA metabolic processes, including replication, recombination, and detection and repair of damage. NABP2 always found in the nucleus, but it also localizes to nuclear foci following DNA damage. Foci formation is not cell-cycle dependent. Otherwise, NABP2 partial colocalized with RAD51 after ionizing radiation treatment. The SOSS complex composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP, while SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1. NABP2 directly interacts with ATM, SOSS-A/INTS3, RAD51 and INTS7.

Gene Function [1-3]

As a component of the SOSS complex, which is a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint, NABP2 plays a role 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. NABP2 required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways.

The relationships between gene and major human diseases

  • NABP2 and the repair of damaged DNA [4]

The maintenance of genome stability is an essential cellular process to prevent the development of diseases including cancer. NABP2 (NABP2/ OBFC2A) is a critical component of the DNA damage response where it participates in the repair of double-strand DNA breaks and in base excision repair of oxidized guanine residues (8-oxoguanine) by aiding the localization of the human 8-oxoguanine glycosylase (hOGG1) to damaged DNA. The study demonstrated that following oxidative stress, NABP2 is stabilized as an oligomer which is required for NABP2 to function in the removal of 8-oxoguanine and demonstrated a novel NABP2 regulatory mechanism for the repair of damaged DNA.

  • NABP2 and hepatocellular carcinomas [5]

Downregulation of NABP2, a single-stranded DNA-binding protein, causes increased radio sensitivity, defective checkpoint activation and genomic instability. Previous study presented evidence that NABP2 directly binds p21 and this interaction may prevent p21 from ubiquitin-mediated degradation. Furthermore, both promotion of the G1/S transition and abrogation of the G2/M checkpoints induced by NABP2 knockdown are partially dependent on p21. Most importantly, NABP2 and p21 levels are positively correlated in human hepatocellular carcinomas (HCC), as determined by immunostaining. Therefore, NABP2 may positively modulate p21 to regulate cell cycle progression and DNA damage response, implicating NABP2 as a novel, promising therapeutic target for cancers such as HCC.

Conclusions

NABP2 was demonstrated to be essential for homologous recombination (HR), which repairs of one of the most lethal types of DNA damage, double-stranded DNA breaks (DSBs). The structures analysis of NABP2 is important in understanding the molecular mechanism of the interaction between NABP2 and ssDNA, especially since blocking ssDNA binding by NABP2 in tumor cells may be of significant interest for the development of novel cancer therapeutics [6].

References:

  1. Richard, D.J., et al., Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature, 2008. 453(7195): p. 677-81.
  2. Li, Y., et al., HSSB1 and hSSB2 form similar multiprotein complexes that participate in DNA damage response. J Biol Chem, 2009. 284(35): p. 23525-31.
  3. Huang, J., et al., SOSS complexes participate in the maintenance of genomic stability. Mol Cell, 2009. 35(3): p. 384-93.
  4. Paquet, N., et al., hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress. Sci Rep, 2016. 6: p. 27446.
  5. Xu, S., et al., hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas. Oncogene, 2011. 30(19): p. 2219-29.
  6. Touma, C., et al., A structural analysis of DNA binding by hSSB1 (NABP2/OBFC2B) in solution. Nucleic Acids Res, 2016. 44(16): p. 7963-73.