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Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination

Homologous recombination (HR) plays an important role in maintaining genomic integrity. It is responsible for repair of the most harmful DNA lesions, DNA double-strand breaks and inter-strand DNA cross-links. HR function is also essential for proper segregation of homologous chromosomes in meiosis,...

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Autores principales: Hanamshet, Kritika, Mazina, Olga M., Mazin, Alexander V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042393/
https://www.ncbi.nlm.nih.gov/pubmed/27649245
http://dx.doi.org/10.3390/genes7090063
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author Hanamshet, Kritika
Mazina, Olga M.
Mazin, Alexander V.
author_facet Hanamshet, Kritika
Mazina, Olga M.
Mazin, Alexander V.
author_sort Hanamshet, Kritika
collection PubMed
description Homologous recombination (HR) plays an important role in maintaining genomic integrity. It is responsible for repair of the most harmful DNA lesions, DNA double-strand breaks and inter-strand DNA cross-links. HR function is also essential for proper segregation of homologous chromosomes in meiosis, maintenance of telomeres, and resolving stalled replication forks. Defects in HR often lead to genetic diseases and cancer. Rad52 is one of the key HR proteins, which is evolutionarily conserved from yeast to humans. In yeast, Rad52 is important for most HR events; Rad52 mutations disrupt repair of DNA double-strand breaks and targeted DNA integration. Surprisingly, in mammals, Rad52 knockouts showed no significant DNA repair or recombination phenotype. However, recent work demonstrated that mutations in human RAD52 are synthetically lethal with mutations in several other HR proteins including BRCA1 and BRCA2. These new findings indicate an important backup role for Rad52, which complements the main HR mechanism in mammals. In this review, we focus on the Rad52 activities and functions in HR and the possibility of using human RAD52 as therapeutic target in BRCA1 and BRCA2-deficient familial breast cancer and ovarian cancer.
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spelling pubmed-50423932016-09-29 Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination Hanamshet, Kritika Mazina, Olga M. Mazin, Alexander V. Genes (Basel) Review Homologous recombination (HR) plays an important role in maintaining genomic integrity. It is responsible for repair of the most harmful DNA lesions, DNA double-strand breaks and inter-strand DNA cross-links. HR function is also essential for proper segregation of homologous chromosomes in meiosis, maintenance of telomeres, and resolving stalled replication forks. Defects in HR often lead to genetic diseases and cancer. Rad52 is one of the key HR proteins, which is evolutionarily conserved from yeast to humans. In yeast, Rad52 is important for most HR events; Rad52 mutations disrupt repair of DNA double-strand breaks and targeted DNA integration. Surprisingly, in mammals, Rad52 knockouts showed no significant DNA repair or recombination phenotype. However, recent work demonstrated that mutations in human RAD52 are synthetically lethal with mutations in several other HR proteins including BRCA1 and BRCA2. These new findings indicate an important backup role for Rad52, which complements the main HR mechanism in mammals. In this review, we focus on the Rad52 activities and functions in HR and the possibility of using human RAD52 as therapeutic target in BRCA1 and BRCA2-deficient familial breast cancer and ovarian cancer. MDPI 2016-09-14 /pmc/articles/PMC5042393/ /pubmed/27649245 http://dx.doi.org/10.3390/genes7090063 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hanamshet, Kritika
Mazina, Olga M.
Mazin, Alexander V.
Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination
title Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination
title_full Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination
title_fullStr Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination
title_full_unstemmed Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination
title_short Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination
title_sort reappearance from obscurity: mammalian rad52 in homologous recombination
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042393/
https://www.ncbi.nlm.nih.gov/pubmed/27649245
http://dx.doi.org/10.3390/genes7090063
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