Russo, Giusi
(2015)
Chromatin modification induced by
DNA damage and repair.
DNA methylation induced by DNA damage and repair causes stochastic variations of gene expression.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
Chromatin modification induced by
DNA damage and repair.
DNA methylation induced by DNA damage and repair causes stochastic variations of gene expression |
| Autori: |
| Autore | Email |
|---|
| Russo, Giusi | russo.giusi84@gmail.com |
|
| Data: |
31 Marzo 2015 |
| Numero di pagine: |
59 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Medicina Molecolare e Biotecnologie Mediche |
| Scuola di dottorato: |
Medicina molecolare |
| Dottorato: |
Patologia e fisiopatologia molecolare |
| Ciclo di dottorato: |
27 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Avvedimento, Vittorio Enrico | avvedim@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Avvedimento, Vittorio Enrico | [non definito] |
|
| Data: |
31 Marzo 2015 |
| Numero di pagine: |
59 |
| Parole chiave: |
DNA damage, DNA methylation, chromatin loops, histone modification,gene silencing |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 06 - Scienze mediche > MED/04 - Patologia generale |
[error in script]
[error in script]
| Depositato il: |
14 Apr 2015 05:55 |
| Ultima modifica: |
07 Mag 2016 01:00 |
| URI: |
http://www.fedoa.unina.it/id/eprint/10474 |
| DOI: |
10.6092/UNINA/FEDOA/10474 |
Abstract
We report the changes in chromatin structure and gene expression after
homology-directed repair (HR) of a DNA double-strand break (DSB). The
histone code at the DSB site undergoes transient changes following DNA
damage, and is stably modified after repair. Chromatin changes are associated
with modification in DNA methylation and local chromatin structure, which
determine the rate of transcription of the repaired gene. During repair discrete
DNA loops form that connect the 5' and the 3' ends of the repaired GFP gene.
Some of these loops are sensitive to RNaseH, suggesting that they are
stabilized by RNA:DNA hybrids. BER-NER enzymes recruited to the DSB
influence the final methylation status of the repaired gene, as does transcription
of the gene during the three weeks following repair. The changes in
methylation patterns are permanent, and can be used to detect the damagerepair
events. We provide three examples of this, comparing the qualitative
methylation profiles of two suppressor genes, frequently methylated in cancer,
and of a neutral gene, GFP.
These data demonstrate that somatic DNA methylation induced by DNA
damage and HR stably modifies local chromatin structure and is a source of
permanent stochastic variation of gene expression in somatic cells.
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