Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
2019
textabstractHomologous recombination (HR) is the principal mechanism of DNA repair acting during
meiosis and is fundamental for the segregation of chromosomes and the increase of genetic
diversity. Nevertheless, non-homologous end joining (NHEJ) mechanisms can also act during meiosis, mainly in response to exogenously-induced DNA damage in late stages of first
meiotic prophase. In order to better understand the relationship between these two repair
pathways, we studied the response to DNA damage during male mouse meiosis after
gamma radiation. We clearly discerned two types of responses immediately after treatment.
From leptotene to early pachytene, exogenous damage triggered the massive presence of
γH2AX throughout the nucleus, which was associated with DNA repair mediated by HR
components (DMC1 and RAD51). This early pathway finished with the sequential removal
of DMC1 and RAD51 and was no longer inducible at mid pachytene. However, from midpachytene to diplotene, γH2AX appeared as large discrete foci. This late repair pattern was
mediated initially by NHEJ, involving Ku70 and XRCC4, which were constitutively present,
and 53BP1, which appeared at sites of damage soon after irradiation. Nevertheless, 24
hours after irradiation, a HR pathway involving RAD51 but not DMC1 mostly replaced
NHEJ. Additionally, we observed the occurrence of synaptonemal complex bridges between
bivalents, most likely representing chromosome translocation events that may involve
DMC1, RAD51 or 53BP1. Our results reinforce the idea that the early “meiotic” repair pathway that acts by default at the beginning of meiosis is replaced from mid-pachytene onwards
by a “somatic-like” repair pattern. This shift might be important to resolve DNA damage
(either endogenous or exogenous) that could not be repaired by the early meiotic mechanisms, for instance those in the sex chromosomes, which lack a homologous chromosome
to repair with. This transition represents another layer of functional changes that occur in
meiotic cells during mid pachytene, in addition to epigenetic reprograming, reactivation of
transcription, changes in the gene expression profile and acquisition of competence to proceed to metaphase.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
100
References
33
Citations
NaN
KQI