THE DNA DAMAGE CHECKPOINT REGULATES MISMATCH REPAIR COMPLEXES DURING SINGLE STRAND ANNEALING PATHWAY
type: CreativeWork
description: By threatening genome stability, endogenous and exogenous sources have the potential to alter the fundamental building blocks of genetic information. The vast majority of lesions are single-strand DNA breaks caused by physiological processes such as DNA replication or oxidative stress during cellular metabolism. Moreover, single-strand DNA breaks can be converted to DNA double-strand breaks (DSBs), which are the most dangerous form of DNA lesions. DSBs are throught to be particularly relevant because their repair is more difficult then other types of DNA damage, potentially leading to chromosome rearrangements and loss of genetic information. Cells evolved multiple pathways to repair DNA anomalies and maintain genome integrity. Moreover, eukaryotic cells respond to DSBs by activating the DNA damage checkpoint (DDC), a surveillance network essential for coordinating a multifaceted response to DNA lesions. Each DSB repair pathway must be coordinated with a series of signalling responses that either halt cell division or cause cell death or adaptation to irreparable lesions. Despite extensive research into DNA repair pathways, many aspects of DSB processing and repair remain unknown. Failures in repair DSB or unfaithful repair can occur when specific DNA repair and/or checkpoint pathways are inactivated, or when lesions exceed the capability of DNA repair mechanisms. Among DSBs repair pathways, Single Strand Annealing (SSA) proceeds via annealing of DNA repeats, resulting in an intermediate with non– homologous 3ꞌ–ended tails (3' NHTs) that are removed by the Rad1 – Rad10 (human XPF – ERCC1) endonuclease complex together with Saw1 and Slx4. Furthermore, Slx4 with Rtt107 limits the binding of the DDC mediator Rad9/53BP1 in proximity of the DSB, reducing checkpoint signalling. We observed that the deletion of RAD9 gene rescues the defects in SSA of both rad1Δ and slx4Δ mutant cells. Therefore, we hypothesized that the DDC limits the activity of a nuclease and/or pathway …
abstract: By threatening genome stability, endogenous and exogenous sources have the potential to alter the fundamental building blocks of genetic information. The vast majority of lesions are single-strand DNA breaks caused by physiological processes such as DNA replication or oxidative stress during cellular metabolism. Moreover, single-strand DNA breaks can be converted to DNA double-strand breaks (DSBs), which are the most dangerous form of DNA lesions. DSBs are throught to be particularly relevant because their repair is more difficult then other types of DNA damage, potentially leading to chromosome rearrangements and loss of genetic information. Cells evolved multiple pathways to repair DNA anomalies and maintain genome integrity. Moreover, eukaryotic cells respond to DSBs by activating the DNA damage checkpoint (DDC), a surveillance network essential for coordinating a multifaceted response to DNA lesions. Each DSB repair pathway must be coordinated with a series of signalling responses that either halt cell division or cause cell death or adaptation to irreparable lesions. Despite extensive research into DNA repair pathways, many aspects of DSB processing and repair remain unknown. Failures in repair DSB or unfaithful repair can occur when specific DNA repair and/or checkpoint pathways are inactivated, or when lesions exceed the capability of DNA repair mechanisms. Among DSBs repair pathways, Single Strand Annealing (SSA) proceeds via annealing of DNA repeats, resulting in an intermediate with non– homologous 3ꞌ–ended tails (3' NHTs) that are removed by the Rad1 – Rad10 (human XPF – ERCC1) endonuclease complex together with Saw1 and Slx4. Furthermore, Slx4 with Rtt107 limits the binding of the DDC mediator Rad9/53BP1 in proximity of the DSB, reducing checkpoint signalling. We observed that the deletion of RAD9 gene rescues the defects in SSA of both rad1Δ and slx4Δ mutant cells. Therefore, we hypothesized that the DDC limits the activity of a nuclease and/or pathway …
author: VIETRI, MARIA YLENIA
language: eng
keywords: Single Strand Annealing, Mismatch repair, Pms1, Rad9, DNA Damage Checkpoint, Saccharomyces cerevisiae, Settore BIO/11 - Biologia Molecolare
date published: 2023-05-16
date modified: 2026-07-27T20:19:10Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/966599

PropertyValue
property ID: DOI
value: 10.13130/vietri-maria-ylenia_phd2023-05-16