Abstract

DNA repair is a well-covered topic as alteration of genetic integrity underlies many pathological conditions and important transgenerational consequences. Surprisingly, the ploidy status is rarely considered although the presence of homologous chromosomes dramatically impacts the repair capacities of cells. This is especially important for the haploid gametes as they must transfer genetic information to the offspring. An understanding of the different mechanisms monitoring genetic integrity in this context is, therefore, essential as differences in repair pathways exist that differentiate the gamete’s role in transgenerational inheritance. Hence, the oocyte must have the most reliable repair capacity while sperm, produced in large numbers and from many differentiation steps, are expected to carry de novo variations. This review describes the main DNA repair pathways with a special emphasis on ploidy. Differences between Saccharomyces cerevisiae and Schizosaccharomyces pombe are especially useful to this aim as they can maintain a diploid and haploid life cycle respectively.

Highlights

  • Maintenance of genome integrity is a permanent cell challenge as both intra- and extracellular conditions can lead to chemical alterations of nucleotides or their sequence

  • While TFIIHSc is already positioned at the lesion in TC-Nucleotide excision repair (NER), a control step is needed in global-genome NER (GG-NER)

  • Syngamy is a critical step since (1) Chromatids from each parent exist in different cellular compartments; (2) Chromatin undergoes major remodelling associated with demethylation; (3) Male derived chromatids are repaired by the oocyte DNA repair machinery [237]

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Summary

Introduction

Maintenance of genome integrity is a permanent cell challenge as both intra- and extracellular conditions can lead to chemical alterations of nucleotides or their sequence. Proper repair mechanisms have evolved so as to maintain a balance between maintenance of cellular function and adaptative processes improving fitness. Germline cells must be especially proficient at this task as diversity must be transmitted while maintaining the gametes’ integrity through the many differentiation steps. Anisogamy, whereby the two sexes produced highly different and specialized haploid gametes, enhances diversity. Ploidy is a key element to consider for genome plasticity or stability. The following review discusses the DNA repair and genome maintenance processes linked to the ploidy state by comparing two unicellular eukaryotes models, yeasts Saccharomyces cerevisiae (S. cerevisiae) and Schizosaccharomyces pombe (S. pombe), while considering the case of the mammalian gametes

General Consideration Regarding Ploidy States
General Mechanism
NER in Yeast
BER in Yeast
MMR in Yeast
DSB Regulation in Mammals
DSB Regulation in Yeast
NHEJ in Yeast
SSA in Yeast
UV Damage Excision Repair
Photolyases
Alternative DNA Repair Approaches in Yeast
Spermatozoa
Oocyte
Findings
Conclusions
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