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...

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Main Authors: Nahid Khalili, Shazrul Fazry, Mahmood, Ibrahim, Ahmed Najm, Ahmad Azfaralariff
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2024
Online Access:http://journalarticle.ukm.my/24752/
http://journalarticle.ukm.my/24752/1/MAE%204.pdf
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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,
building UKM Institutional Repository
collection Online Access
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.
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spelling oai:generic.eprints.org: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/
http://journalarticle.ukm.my/24752/
http://journalarticle.ukm.my/24752/1/MAE%204.pdf