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A DNA repair pathway score predicts survival in human multiple myeloma Vrije Universiteit Brussel

Alboukadel Kassambara, Claire Gourzones-Dmitriev, Surinder S Sahota, Thierry Rème, Jérôme Moreaux, Hartmut Goldschmidt, Angelos Constantinou, Philippe Pasero, Dirk Hose, Bernard Klein, et al.

DNA repair is critical to resolve extrinsic or intrinsic DNA damage to ensure regulated gene transcription and DNA replication. These pathways control repair of double strand breaks, interstrand crosslinks, and nucleotide lesions occurring on single strands. Distinct DNA repair pathways are highly inter-linked for the fast and optimal DNA repair. A deregulation of DNA repair pathways may maintain and promote genetic instability and drug ...

An aphidicolin-block nucleotide excision repair assay measuring DNA incision and repair capacity Vrije Universiteit Brussel

Kim Vande Loock, Ilse Decordier, Roberta Ciardelli, Dominique Haumont, Micheline Volders
The objective of the present study was to develop a cellular phenotype assay for nucleotide excision repair (NER), using benzo[a]pyrene diol epoxide (BPDE) as model mutagen. Since in vitro exposure to BPDE may lead to DNA strand breaks resulting from both direct interaction with DNA and incisions introduced by the repair enzymes, we aimed to discriminate between both types of breaks using the comet assay and quantified the DNA strand breaks ...

DNA repair enzyme genotypes and their toxicologically relevant phenotypes Vrije Universiteit Brussel

Peter Aka, Raluca Mateuca (Born Teodorescu), Micheline Volders
A comprehensive review of studies of polymorphisms in DNA repair genes and associations with cancer risk was undertaken by Goode et al. [1]. In that study the authors concluded that published data were consistent with associations between: (a) the 8-oxoguanine-DNA glycosylase
(hOGG1) Ser326Cys variant genotype and increased risk of various types of cancer; (b) the X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp variant genotype ...

Preterm newborns show slower repair of oxidative damage and paternal smoking associated DNA damage Vrije Universiteit Brussel

Kim Vande Loock, Roberta Ciardelli, Ilse Decordier, Gina Plas, Micheline Volders
Newborns have to cope with hypoxia during delivery and a sudden increase in oxygen at birth. Oxygen will partly be released as reactive oxygen species having the potential to cause damage to DNA and proteins. In utero, increase of most (non)-enzymatic antioxidants occurs during last weeks of gestation, making preterm neonates probably more sensitive to oxidative stress. Moreover, it has been hypothesized that oxidative stress might be the common ...

RNF4 is required for DNA double-strand break repair in vivo KU Leuven Ghent University

Rajesh Vyas, Peter Kalev, Anna Sablina, Chris Marine
Unrepaired DNA double-strand breaks (DSBs) cause genetic instability that leads to malignant transformation or cell death. Cells respond to DSBs with the ordered recruitment of signaling and repair proteins to the sites of DNA lesions. Coordinated protein SUMOylation and ubiquitylation have crucial roles in regulating the dynamic assembly of protein complexes at these sites. However, how SUMOylation influences protein ubiquitylation at DSBs is ...

Non-muscle invasive bladder cancer tissues have increased base excision repair capacity Hasselt University

Berna Somuncu, Selcuk Keskin, Fatma Merve Antmen, Yesim Saglican, Aysegul Ekmekcioglu, Tugce Ertuzun, Mustafa Bilal Tuna, Can Obek, David WILSON, Umit Ince, et al.
The molecular mechanisms underlying the development and progression of bladder cancer (BC) are complex and have not been fully elucidated. Alterations in base excision repair (BER) capacity, one of several DNA repair mechanisms assigned to preserving genome integrity, have been reported to influence cancer susceptibility, recurrence, and progression, as well as responses to chemotherapy and radiotherapy. We report herein that non-muscle invasive ...

LEO1 is a partner for Cockayne syndrome protein B (CSB) in response to transcription-blocking DNA damage Hasselt University

V Tiwari, T Kulikowicz, David WILSON, VA Bohr
Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) and ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381Ser568 region) as an interacting protein partner of full-length ...

Genetic susceptibility of newborns for DNA damage Vrije Universiteit Brussel

Kim Vande Loock
Despite many efforts made to improve human health, incidence in childhood cancer is increasing and relevant data regarding biomonitoring of newborns to unintended mutagen exposure are lacking. The overall goal of this thesis was to assess the susceptibility of newborns (preterm and full term) to mutagens by comparison with their mothers using biomarkers of exposure, effect and susceptibility in well characterized small Belgian and large European ...

TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo KU Leuven

Lieve Umans, Danny Huylebroeck
Anticancer topoisomerase "poisons" exploit the break-and-rejoining mechanism of topoisomerase II (TOP2) to generate TOP2-linked DNA double-strand breaks (DSBs). This characteristic underlies the clinical efficacy of TOP2 poisons, but is also implicated in chromosomal translocations and genome instability associated with secondary, treatment-related, haematological malignancy. Despite this relevance for cancer therapy, the mechanistic aspects ...

Lynch syndrome caused by germline PMS2 mutations Vrije Universiteit Brussel

Sanne W Ten Broeke, Richard M Brohet, Carli Mj Tops, Heleen M van der Klift, Mary E Velthuizen, Inge Bernstein, Gabriel Capellá Munar, Encarna Gomez Garcia, Nicoline Hoogerbrugge, Tom G W Letteboer, et al.

PURPOSE: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers.

METHODS: Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To ...