Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.

Telomere capture, a rare event that stabilizes chromosome breaks, is associated with certain genetic abnormalities in humans. Studies pertaining to the generation, maintenance, and biological effects of telomere formation are limited in metazoans. A mutation, mu2(a), in Drosophila melanogaster decre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Raghuvar Dronamraju, James M Mason
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/d765feab521342e99c57738fe1a63a3d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d765feab521342e99c57738fe1a63a3d
record_format	dspace
spelling	oai:doaj.org-article:d765feab521342e99c57738fe1a63a3d2021-11-25T05:53:27ZRecognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.1553-73901553-740410.1371/journal.pgen.1000473https://doaj.org/article/d765feab521342e99c57738fe1a63a3d2009-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19424425/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Telomere capture, a rare event that stabilizes chromosome breaks, is associated with certain genetic abnormalities in humans. Studies pertaining to the generation, maintenance, and biological effects of telomere formation are limited in metazoans. A mutation, mu2(a), in Drosophila melanogaster decreases the rate of repair of double strand DNA breaks in oocytes, thus leading to chromosomes that have lost a natural telomere and gained a new telomere. Amino acid sequence, domain architecture, and protein interactions suggest that MU2 is an ortholog of human MDC1. The MU2 protein is a component of meiotic recombination foci and localizes to repair foci in S2 cells after irradiation in a manner similar to that of phosphorylated histone variant H2Av. Domain searches indicated that the protein contains an N-terminal FHA domain and a C-terminal tandem BRCT domain. Peptide pull-down studies showed that the BRCT domain interacts with phosphorylated H2Av, while the FHA domain interacts with the complex of MRE11, RAD50, and NBS. A frameshift mutation that eliminates the MU2 BRCT domain decreases the number and size of meiotic phospho-H2Av foci. MU2 is also required for the intra-S checkpoint in eye-antennal imaginal discs. MU2 participates at an early stage in the recognition of DNA damage at a step that is prerequisite for both DNA repair and cell cycle checkpoint control. We propose a model suggesting that neotelomeres may arise when radiation-induced chromosome breaks fail to be repaired, fail to arrest progression through meiosis, and are deposited in the zygote, where cell cycle control is absent and rapid rounds of replication and telomere formation ensue.Raghuvar DronamrajuJames M MasonPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 5, Iss 5, p e1000473 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Raghuvar Dronamraju James M Mason Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.
description	Telomere capture, a rare event that stabilizes chromosome breaks, is associated with certain genetic abnormalities in humans. Studies pertaining to the generation, maintenance, and biological effects of telomere formation are limited in metazoans. A mutation, mu2(a), in Drosophila melanogaster decreases the rate of repair of double strand DNA breaks in oocytes, thus leading to chromosomes that have lost a natural telomere and gained a new telomere. Amino acid sequence, domain architecture, and protein interactions suggest that MU2 is an ortholog of human MDC1. The MU2 protein is a component of meiotic recombination foci and localizes to repair foci in S2 cells after irradiation in a manner similar to that of phosphorylated histone variant H2Av. Domain searches indicated that the protein contains an N-terminal FHA domain and a C-terminal tandem BRCT domain. Peptide pull-down studies showed that the BRCT domain interacts with phosphorylated H2Av, while the FHA domain interacts with the complex of MRE11, RAD50, and NBS. A frameshift mutation that eliminates the MU2 BRCT domain decreases the number and size of meiotic phospho-H2Av foci. MU2 is also required for the intra-S checkpoint in eye-antennal imaginal discs. MU2 participates at an early stage in the recognition of DNA damage at a step that is prerequisite for both DNA repair and cell cycle checkpoint control. We propose a model suggesting that neotelomeres may arise when radiation-induced chromosome breaks fail to be repaired, fail to arrest progression through meiosis, and are deposited in the zygote, where cell cycle control is absent and rapid rounds of replication and telomere formation ensue.
format	article
author	Raghuvar Dronamraju James M Mason
author_facet	Raghuvar Dronamraju James M Mason
author_sort	Raghuvar Dronamraju
title	Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.
title_short	Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.
title_full	Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.
title_fullStr	Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.
title_full_unstemmed	Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.
title_sort	recognition of double strand breaks by a mutator protein (mu2) in drosophila melanogaster.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/d765feab521342e99c57738fe1a63a3d
work_keys_str_mv	AT raghuvardronamraju recognitionofdoublestrandbreaksbyamutatorproteinmu2indrosophilamelanogaster AT jamesmmason recognitionofdoublestrandbreaksbyamutatorproteinmu2indrosophilamelanogaster
_version_	1718414430801231872

Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster.

Ejemplares similares