La proteína de unión a ácidos nucleicos 1 es una proteína específica que en humanos está codificada por el gen NABP1 . NABP1 (proteína de unión a ácidos nucleicos 1), también conocida como hSSB2, es una proteína presente en humanos que desempeña un papel importante en el mantenimiento de la estabilidad del genoma. [ 5 ] También pertenece a un grupo de proteínas que pueden unirse a la cadena simple de ADN y se forma comúnmente durante la replicación del ADN y los procesos de reparación. [ 6 ] NABP1 es especialmente importante en la respuesta celular al daño del ADN, donde ayuda a reclutar y organizar otras proteínas de reparación en ciertos sitios de daño. [ 7 ] NABP1 también puede contribuir a procesos como la recombinación homóloga y la protección del genoma contra la inestabilidad creada por las enzimas circundantes. [ 8 ] Debido a su importante papel en la reparación del ADN, NABP1 también se ha estudiado por su importante implicación en el cáncer y otras enfermedades relacionadas con la inestabilidad genómica. [ 9 ] [ 10 ] [ 11 ]
Información sobre genes y proteínas
El gen NABP1 codifica específicamente la proteína de unión a ácidos nucleicos 1, una proteína de unión a ADN monocatenario que también se encuentra en células humanas. Esta proteína también se conoce comúnmente como hSSB2 u OBFC2A. NABP1 pertenece a una familia de proteínas implicadas en procesos celulares importantes como la replicación , la recombinación y la reparación del ADN . Estas proteínas también pueden ayudar a estabilizar las hebras de ADN expuestas y prevenir el daño durante la actividad celular normal. [ 12 ]
Estructura
La proteína NABP1 contiene un dominio de unión a oligonucleótidos/oligosacáridos (dominio OB) conservado, que es la parte de la proteína que le permite unirse al ADN monocatenario. Esta estructura también permite que la proteína interactúe directamente con el ADN expuesto durante procesos como la replicación y la reparación del ADN . El dominio OB también se encuentra en muchas otras proteínas de unión a ADN monocatenario, lo que demuestra su importancia para mantener la estabilidad y el funcionamiento del genoma . [9] [ 13 ]


Función biológica
As known before NABP1 plays a very important role in helping keep the genome stable. It does this by binding to single stranded DNA and also by protecting it from damage. It is also involved in many important cellular processes like DNA replication and cell recombination like stated before. This is really where the DNA is either copied or even rearranged. When they then are attached to the exposed DNA strands the NABP1 protein can then help keep the DNA in the correct shape so that it can be copied and then also repaired in the right way.[14]
Also as discussed before NABP1 mainly will work by mainly binding to the regions of single stranded DNA that become very exposed during these normal cellular processes that are going on in the cell. Then these exposed areas are way more likely to be damaged and even so they need to be protected. When the NABP1 binds to these regions it stabilizes the DNA and prevents it from forming the wrong structures or even being degraded by some nucleases. This also will be easier for other proteins in the cell to come in and do their jobs correctly.[15]
NABP1 does play an important role in replication but it is also involved in recombination and also in responding to the replication stress. This really happens when DNA copying is disrupted or degraded. It helps specifically organize and support the tasks of other proteins that are needed for these processes. Also by working hard together with these other proteins the NABP1 that DNA is handled correctly and that the mistakes are rare during these important cellular events. The problem is that if NABP1 is not working properly then the cell can start to build up DNA damage. Genomic instability can be caused by this which is when the DNA becomes more prone to mutations or errors and will cause the cell to die. These kinds of the problems can affect how the cells grow and divide and could even contribute to the bad diseases like cancer. NABP1 is considered an important protein for maintaining the normal cell function and the overall cellular health.[16][17]
Role in DNA damage response
NABP1 does play a very key role in the cellular response to DNA damage specifically in the situations where the DNA strands are broken and/or exposed out of their pocket. When DNA damage occurs there are regions of the single stranded DNA created which then signals the repair processes to begin. NABP1 then can bind to these exposed regions and helps to stabilize them so that they can also be repaired. After the binding to the damaged DNA NABP1 then helps recruit other proteins that are also involved in DNA repair pathways like homologous recombination. This process is also very important for accurately repairing double strand breaks in DNA. NABP1 can also work then with protein complexes such as the SOSS complex this then helps coordinate the repair response and also ensure that DNA damage is resolved. NABP1 is also involved in signaling pathways that can activate the main DNA damage response. It can help activate proteins like ATM kinase. The ATM kinase plays a major role in controlling the cell cycle checkpoints and repair mechanisms. NABP1 helps cells respond to DNA damage and maintain genomic stability in these checkpoints and processes.
Interaction partners
NABP1 does not just function alone but it can actually interact with several other proteins to help carry out its role in DNA repair. The main partner it has that helps its functions is INTS3. INTS3 will help stabilize specifically NABP1 and also can regulate its activity. NABP1 also can help interact with a protein called C9orf80 and these proteins form part of a larger complex that is involved in DNA damage response. These protein interactions are important because DNA repair does require multiple proteins working together in a coordinated way. NABP1 helps get these proteins to the right sites of DNA damage and supports their activity. Without these interactions between these proteins the repair process would be less efficient and more prone to errors. [18]
Clinical significance
There have been many links between mutations or alterations within the NABP1 protein and certain cellular diseases like cancer. It is known that when processes like cellular repair fail that many problems can occur like mutations which will cause the cell to have problems growing and replicating which will lead to death. Mutations and other instability within the genome are the main causes of cancer. DNA repair is a process that requires multiple proteins and multiple complexes that need to come together with a common goal in mind which is to repair the DNA. NABP1 will help and coordinate the ways that these proteins are brought in and also will make sure they are actually going to the right place. [19]
References
- 123GRCh38: Ensembl release 89: ENSG00000173559–Ensembl, May 2017
- 123GRCm38: Ensembl release 89: ENSMUSG00000026107–Ensembl, May 2017
- ↑"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑Richard, DJ (2008). "Single-stranded DNA-binding protein hSSB1 is critical for the genomic stability". Nature. 453: 677–681.
- ↑Oakley, GG (2010). "Replication protein A: directing traffic at the intersection of replication and repair". Frontiers in Bioscience.
- ↑Jackson, SP (2009). "The DNA-damage response in human biology and disease". Nature.
- ↑Richard, DJ (2008). "Single-stranded DNA-binding protein hSSB1 is critical for genomic stability". Nature. 453: 677–681.
- ↑Negrini, S (2010). "Genomic instability—an evolving hallmark of cancer". Nature Reviews Molecular Cell Biology.
- ↑Jackson, SP (2009). "The DNA-damage response in human biology and disease". Nature.
- ↑"Entrez Gene: Nucleic acid binding protein 1".
- ↑Richard, DJ (2008). "Single-stranded DNA-binding protein hSSB1 is critical for genomic stability". Nature. 453: 677–681.
- ↑Oakley, GG (2010). "Replication protein A: directing traffic at the intersection of replication and repair". Frontiers in Bioscience.
- ↑Richard, DJ (2008). "Single-stranded DNA-binding protein hSSB1 is critical for genomic stability". Nature. 453: 677–681.
- ↑Oakley, GG (2010). "Replication protein A: directing traffic at the intersection of replication and repair". Frontiers in Bioscience.
- ↑Branzei, D (2008). "Replication stress and DNA damage tolerance". Nature Reviews Molecular Cell Biology.
- ↑Negrini, S (2010). "Genomic instability—an evolving hallmark of cancer". Nature Reviews Molecular Cell Biology.
- ↑Huang, J (2009). "SOSS complexes participate in the maintenance of genomic stability". Molecular Cell.
- ↑Jackson, SP (2009). "The DNA-damage response in human biology and disease". Nature.
Further reading
- Li Y, Bolderson E, Kumar R, Muniandy PA, Xue Y, Richard DJ, Seidman M, Pandita TK, Khanna KK, Wang W (August 2009). "HSSB1 and hSSB2 form similar multiprotein complexes that participate in DNA damage response". The Journal of Biological Chemistry. 284 (35): 23525–31. doi:10.1074/jbc.C109.039586. PMC 2749126. PMID 19605351.
- Huang J, Gong Z, Ghosal G, Chen J (August 2009). "SOSS complexes participate in the maintenance of genomic stability". Molecular Cell. 35 (3): 384–93. doi:10.1016/j.molcel.2009.06.011. PMC 2756616. PMID 19683501.
- Malovannaya A, Li Y, Bulynko Y, Jung SY, Wang Y, Lanz RB, O'Malley BW, Qin J (febrero de 2010). "Esquema de análisis simplificado para la identificación de alto rendimiento de complejos proteicos endógenos" . Actas de la Academia Nacional de Ciencias de los Estados Unidos de América . 107 (6): 2431– 6. Bibcode : 2010PNAS..107.2431M . doi : 10.1073/pnas.0912599106 . PMC 2823922. PMID 20133760 .
Este artículo incorpora texto de la Biblioteca Nacional de Medicina de los Estados Unidos , que es de dominio público .
- Genes en el cromosoma 2 humano