A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.

RNA polymerase II translocates across much of the genome and since it can be blocked by many kinds of DNA lesions, detects DNA damage proficiently; it thereby contributes to DNA repair and to normal levels of DNA damage resistance. However, the components and mechanisms that respond to polymerase bl...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tiffany Sabin Winsor, Bartlomiej Bartkowiak, Craig B Bennett, Arno L Greenleaf
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/842d140183d0487fa03126abb5f4214f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:842d140183d0487fa03126abb5f4214f
record_format	dspace
spelling	oai:doaj.org-article:842d140183d0487fa03126abb5f4214f2021-11-18T07:49:23ZA DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.1932-620310.1371/journal.pone.0060909https://doaj.org/article/842d140183d0487fa03126abb5f4214f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23613755/?tool=EBIhttps://doaj.org/toc/1932-6203RNA polymerase II translocates across much of the genome and since it can be blocked by many kinds of DNA lesions, detects DNA damage proficiently; it thereby contributes to DNA repair and to normal levels of DNA damage resistance. However, the components and mechanisms that respond to polymerase blockage are largely unknown, except in the case of UV-induced damage that is corrected by nucleotide excision repair. Because elongating RNAPII carries with it numerous proteins that bind to its hyperphosphorylated CTD, we tested for effects of interfering with this binding. We find that expressing a decoy CTD-carrying protein in the nucleus, but not in the cytoplasm, leads to reduced DNA damage resistance. Likewise, inducing aberrant phosphorylation of the CTD, by deleting CTK1, reduces damage resistance and also alters rates of homologous recombination-mediated repair. In line with these results, extant data sets reveal a remarkable, highly significant overlap between phosphoCTD-associating protein genes and DNA damage-resistance genes. For one well-known phosphoCTD-associating protein, the histone methyltransferase Set2, we demonstrate a role in DNA damage resistance, and we show that this role requires the phosphoCTD binding ability of Set2; surprisingly, Set2's role in damage resistance does not depend on its catalytic activity. To explain all of these observations, we posit the existence of a CTD-Associated DNA damage Response (CAR) system, organized around the phosphoCTD of elongating RNAPII and comprising a subset of phosphoCTD-associating proteins.Tiffany Sabin WinsorBartlomiej BartkowiakCraig B BennettArno L GreenleafPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60909 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiffany Sabin Winsor Bartlomiej Bartkowiak Craig B Bennett Arno L Greenleaf A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.
description	RNA polymerase II translocates across much of the genome and since it can be blocked by many kinds of DNA lesions, detects DNA damage proficiently; it thereby contributes to DNA repair and to normal levels of DNA damage resistance. However, the components and mechanisms that respond to polymerase blockage are largely unknown, except in the case of UV-induced damage that is corrected by nucleotide excision repair. Because elongating RNAPII carries with it numerous proteins that bind to its hyperphosphorylated CTD, we tested for effects of interfering with this binding. We find that expressing a decoy CTD-carrying protein in the nucleus, but not in the cytoplasm, leads to reduced DNA damage resistance. Likewise, inducing aberrant phosphorylation of the CTD, by deleting CTK1, reduces damage resistance and also alters rates of homologous recombination-mediated repair. In line with these results, extant data sets reveal a remarkable, highly significant overlap between phosphoCTD-associating protein genes and DNA damage-resistance genes. For one well-known phosphoCTD-associating protein, the histone methyltransferase Set2, we demonstrate a role in DNA damage resistance, and we show that this role requires the phosphoCTD binding ability of Set2; surprisingly, Set2's role in damage resistance does not depend on its catalytic activity. To explain all of these observations, we posit the existence of a CTD-Associated DNA damage Response (CAR) system, organized around the phosphoCTD of elongating RNAPII and comprising a subset of phosphoCTD-associating proteins.
format	article
author	Tiffany Sabin Winsor Bartlomiej Bartkowiak Craig B Bennett Arno L Greenleaf
author_facet	Tiffany Sabin Winsor Bartlomiej Bartkowiak Craig B Bennett Arno L Greenleaf
author_sort	Tiffany Sabin Winsor
title	A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.
title_short	A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.
title_full	A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.
title_fullStr	A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.
title_full_unstemmed	A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.
title_sort	dna damage response system associated with the phosphoctd of elongating rna polymerase ii.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/842d140183d0487fa03126abb5f4214f
work_keys_str_mv	AT tiffanysabinwinsor adnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii AT bartlomiejbartkowiak adnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii AT craigbbennett adnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii AT arnolgreenleaf adnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii AT tiffanysabinwinsor dnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii AT bartlomiejbartkowiak dnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii AT craigbbennett dnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii AT arnolgreenleaf dnadamageresponsesystemassociatedwiththephosphoctdofelongatingrnapolymeraseii
_version_	1718422922331160576

A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II.

Ejemplares similares