Next Article in Journal / Special Issue
Repetitive Fragile Sites: Centromere Satellite DNA as a Source of Genome Instability in Human Diseases
Previous Article in Journal
Generation of A Mucor circinelloides Reporter Strain—A Promising New Tool to Study Antifungal Drug Efficacy and Mucormycosis
Previous Article in Special Issue
Homologous Recombination: To Fork and Beyond
Article Menu

Article Versions

Export Article

Open AccessReview
Genes 2018, 9(12), 614; https://doi.org/10.3390/genes9120614

DNA Damage Tolerance Mechanisms Revealed from the Analysis of Immunoglobulin V Gene Diversification in Avian DT40 Cells

1
Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo 192-0397, Japan
2
IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
3
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (IGM-CNR), Via Abbiategrasso 207, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Received: 30 October 2018 / Revised: 26 November 2018 / Accepted: 30 November 2018 / Published: 7 December 2018
(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)
PDF [716 KB, uploaded 7 December 2018]   |   Review Reports

Abstract

DNA replication is an essential biochemical reaction in dividing cells that frequently stalls at damaged sites. Homologous/homeologous recombination (HR)-mediated template switch and translesion DNA synthesis (TLS)-mediated bypass processes release arrested DNA replication forks. These mechanisms are pivotal for replication fork maintenance and play critical roles in DNA damage tolerance (DDT) and gap-filling. The avian DT40 B lymphocyte cell line provides an opportunity to examine HR-mediated template switch and TLS triggered by abasic sites by sequencing the constitutively diversifying immunoglobulin light-chain variable gene (IgV). During IgV diversification, activation-induced deaminase (AID) converts dC to dU, which in turn is excised by uracil DNA glycosylase and yields abasic sites within a defined window of around 500 base pairs. These abasic sites can induce gene conversion with a set of homeologous upstream pseudogenes via the HR-mediated template switch, resulting in templated mutagenesis, or can be bypassed directly by TLS, resulting in non-templated somatic hypermutation at dC/dG base pairs. In this review, we discuss recent works unveiling IgV diversification mechanisms in avian DT40 cells, which shed light on DDT mode usage in vertebrate cells and tolerance of abasic sites.
Keywords: homologous recombination; translesion DNA synthesis; replication; activation-induced deaminase; abasic site; DNA damage homologous recombination; translesion DNA synthesis; replication; activation-induced deaminase; abasic site; DNA damage
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Abe, T.; Branzei, D.; Hirota, K. DNA Damage Tolerance Mechanisms Revealed from the Analysis of Immunoglobulin V Gene Diversification in Avian DT40 Cells. Genes 2018, 9, 614.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top