RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms
The MRE11-RAD50-NBS1 (MRN) complex is essential in detecting, signaling, and repairing DNA double-strand breaks (DSBs), thus maintaining genomic integrity. Mutations in RAD50 are linked to severe conditions such as microcephaly, mental retardation, and growth retardation in humans. This study invest...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Penerbit Universiti Kebangsaan Malaysia
2024
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| Online Access: | http://journalarticle.ukm.my/24752/1/MAE%204.pdf |
| _version_ | 1824449807017574400 |
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| author | Nahid Khalili, Shazrul Fazry, Mahmood, Ibrahim Ahmed Najm, Ahmad Azfaralariff, |
| author_facet | Nahid Khalili, Shazrul Fazry, Mahmood, Ibrahim Ahmed Najm, Ahmad Azfaralariff, |
| author_sort | Nahid Khalili, |
| collection | UKM |
| description | The MRE11-RAD50-NBS1 (MRN) complex is essential in detecting, signaling, and repairing DNA double-strand breaks (DSBs), thus maintaining genomic integrity. Mutations in RAD50 are linked to severe conditions such as microcephaly, mental retardation, and growth retardation in humans. This study investigates the developmental impact of RAD50 protein disruption in zebrafish embryos. Zebrafish embryos were treated with MIRIN (35 μM) to inhibit RAD50 and subsequently exposed to gamma-ray irradiation (15 Gy) to analyze the role of RAD50 in managing DNA damage during embryogenesis. Time-point analysis indicated that inhibiting RAD50 and ATM proteins during early embryonic stages (at 1 hpf) leads to increased embryonic mortality and abnormalities. These adverse effects were exacerbated by irradiation, underscoring the critical role of RAD50 in DNA DSB repair. The study concludes that RAD50 deficiencies can lead to embryonic lethality and human deformities due to the inability of tissues to repair DNA DSBs effectively. |
| first_indexed | 2025-02-19T02:08:42Z |
| format | Article |
| id | ukm.eprints-24752 |
| institution | Universiti Kebangsaan Malaysia |
| language | English |
| last_indexed | 2025-02-19T02:08:42Z |
| publishDate | 2024 |
| publisher | Penerbit Universiti Kebangsaan Malaysia |
| record_format | dspace |
| spelling | ukm.eprints-247522025-01-23T04:37:24Z http://journalarticle.ukm.my/24752/ RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms Nahid Khalili, Shazrul Fazry, Mahmood, Ibrahim Ahmed Najm, Ahmad Azfaralariff, The MRE11-RAD50-NBS1 (MRN) complex is essential in detecting, signaling, and repairing DNA double-strand breaks (DSBs), thus maintaining genomic integrity. Mutations in RAD50 are linked to severe conditions such as microcephaly, mental retardation, and growth retardation in humans. This study investigates the developmental impact of RAD50 protein disruption in zebrafish embryos. Zebrafish embryos were treated with MIRIN (35 μM) to inhibit RAD50 and subsequently exposed to gamma-ray irradiation (15 Gy) to analyze the role of RAD50 in managing DNA damage during embryogenesis. Time-point analysis indicated that inhibiting RAD50 and ATM proteins during early embryonic stages (at 1 hpf) leads to increased embryonic mortality and abnormalities. These adverse effects were exacerbated by irradiation, underscoring the critical role of RAD50 in DNA DSB repair. The study concludes that RAD50 deficiencies can lead to embryonic lethality and human deformities due to the inability of tissues to repair DNA DSBs effectively. Penerbit Universiti Kebangsaan Malaysia 2024 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/24752/1/MAE%204.pdf Nahid Khalili, and Shazrul Fazry, and Mahmood, Ibrahim and Ahmed Najm, and Ahmad Azfaralariff, (2024) RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms. Malaysian Applied Biology, 53 (4). pp. 27-42. ISSN 0126-8643 https://jms.mabjournal.com/index.php/mab/issue/view/63 |
| spellingShingle | Nahid Khalili, Shazrul Fazry, Mahmood, Ibrahim Ahmed Najm, Ahmad Azfaralariff, RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms |
| title | RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms |
| title_full | RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms |
| title_fullStr | RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms |
| title_full_unstemmed | RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms |
| title_short | RAD50 deficiency and its effects on zebrafish embryonic development and DNA repair mechanisms |
| title_sort | rad50 deficiency and its effects on zebrafish embryonic development and dna repair mechanisms |
| url | http://journalarticle.ukm.my/24752/1/MAE%204.pdf |
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