Descoberto novo mecanismo de reparo do DNA: mais complexidade que Darwin não explica!

sábado, julho 04, 2015

Structure of transcribed chromatin is a sensor of DNA damage

Nikolay A. Pestov1,*, Nadezhda S. Gerasimova2,*, Olga I. Kulaeva2,3 and Vasily M. Studitsky1,2,3,†

+ Author Affiliations

↵†Corresponding author. E-mail: vasily.studitsky@fccc.edu

↵* These authors contributed equally to this work.

Science Advances 03 Jul 2015:

Vol. 1, no. 6, e1500021

DOI: 10.1126/sciadv.1500021

Article



Abstract

Early detection and repair of damaged DNA is essential for cell functioning and survival. Although multiple cellular systems are involved in the repair of single-strand DNA breaks (SSBs), it remains unknown how SSBs present in the nontemplate strand (NT-SSBs) of DNA organized in chromatin are detected. The effect of NT-SSBs on transcription through chromatin by RNA polymerase II was studied. NT-SSBs localized in the promoter-proximal region of nucleosomal DNA and hidden in the nucleosome structure can induce a nearly quantitative arrest of RNA polymerase downstream of the break, whereas more promoter-distal SSBs moderately facilitate transcription. The location of the arrest sites on nucleosomal DNA suggests that formation of small intranucleosomal DNA loops causes the arrest. This mechanism likely involves relief of unconstrained DNA supercoiling accumulated during transcription through chromatin by NT-SSBs. These data suggest the existence of a novel chromatin-specific mechanism that allows the detection of NT-SSBs by the transcribing enzyme.

Keywords DNA damage chromatin structure transcription-coupled DNA repair single-strand DNA breaks DNA loop nucleosome

Copyright © 2015, The Authors

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

FREE PDF GRATIS: Science Advances