Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis
Nijmegen breakage syndrome (NBS) is a recessive genetic disorder characterized by increased sensitivity to ionizing radiation (IR) and a high frequency of malignancies. NBS1, a product of the mutated gene in NBS, contains several protein interaction domains in the N-terminus and C-terminus. The C-te...
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MDPI AG
2015-08-01
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| Series: | Biomolecules |
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| Online Access: | http://www.mdpi.com/2218-273X/5/3/1990 |
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| author | Yuichiro Saito Kenshi Komatsu |
| author_facet | Yuichiro Saito Kenshi Komatsu |
| author_sort | Yuichiro Saito |
| collection | DOAJ |
| description | Nijmegen breakage syndrome (NBS) is a recessive genetic disorder characterized by increased sensitivity to ionizing radiation (IR) and a high frequency of malignancies. NBS1, a product of the mutated gene in NBS, contains several protein interaction domains in the N-terminus and C-terminus. The C-terminus of NBS1 is essential for interactions with MRE11, a homologous recombination repair nuclease, and ATM, a key player in signal transduction after the generation of DNA double-strand breaks (DSBs), which is induced by IR. Moreover, NBS1 regulates chromatin remodeling during DSB repair by histone H2B ubiquitination through binding to RNF20 at the C-terminus. Thus, NBS1 is considered as the first protein to be recruited to DSB sites, wherein it acts as a sensor or mediator of DSB damage responses. In addition to DSB response, we showed that NBS1 initiates Polη-dependent translesion DNA synthesis by recruiting RAD18 through its binding at the NBS1 C-terminus after UV exposure, and it also functions after the generation of interstrand crosslink DNA damage. Thus, NBS1 has multifunctional roles in response to DNA damage from a variety of genotoxic agents, including IR. |
| first_indexed | 2024-12-21T13:51:44Z |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-21T13:51:44Z |
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| spelling | doaj.art-b6c0140f99464e7abe10101dd6850f302022-12-21T19:01:41ZengMDPI AGBiomolecules2218-273X2015-08-01531990200210.3390/biom5031990biom5031990Functional Role of NBS1 in Radiation Damage Response and Translesion DNA SynthesisYuichiro Saito0Kenshi Komatsu1Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, JapanGenome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, JapanNijmegen breakage syndrome (NBS) is a recessive genetic disorder characterized by increased sensitivity to ionizing radiation (IR) and a high frequency of malignancies. NBS1, a product of the mutated gene in NBS, contains several protein interaction domains in the N-terminus and C-terminus. The C-terminus of NBS1 is essential for interactions with MRE11, a homologous recombination repair nuclease, and ATM, a key player in signal transduction after the generation of DNA double-strand breaks (DSBs), which is induced by IR. Moreover, NBS1 regulates chromatin remodeling during DSB repair by histone H2B ubiquitination through binding to RNF20 at the C-terminus. Thus, NBS1 is considered as the first protein to be recruited to DSB sites, wherein it acts as a sensor or mediator of DSB damage responses. In addition to DSB response, we showed that NBS1 initiates Polη-dependent translesion DNA synthesis by recruiting RAD18 through its binding at the NBS1 C-terminus after UV exposure, and it also functions after the generation of interstrand crosslink DNA damage. Thus, NBS1 has multifunctional roles in response to DNA damage from a variety of genotoxic agents, including IR.http://www.mdpi.com/2218-273X/5/3/1990NBS1DNA repairhomologous recombinationchromatin remodelingtranslesion DNA synthesis |
| spellingShingle | Yuichiro Saito Kenshi Komatsu Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis Biomolecules NBS1 DNA repair homologous recombination chromatin remodeling translesion DNA synthesis |
| title | Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis |
| title_full | Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis |
| title_fullStr | Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis |
| title_full_unstemmed | Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis |
| title_short | Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis |
| title_sort | functional role of nbs1 in radiation damage response and translesion dna synthesis |
| topic | NBS1 DNA repair homologous recombination chromatin remodeling translesion DNA synthesis |
| url | http://www.mdpi.com/2218-273X/5/3/1990 |
| work_keys_str_mv | AT yuichirosaito functionalroleofnbs1inradiationdamageresponseandtranslesiondnasynthesis AT kenshikomatsu functionalroleofnbs1inradiationdamageresponseandtranslesiondnasynthesis |