ATR signaling in mammalian meiosis: From upstream scaffolds to downstream signaling

In germ cells undergoing meiosis, the induction of double strand breaks (DSBs) is required for the generation of haploid gametes. Defects in the formation, detection, or recombinational repair of DSBs often result in defective chromosome segregation and aneuploidies. Central to the ability of meioti...

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Bibliographic Details
Published in:Environmental and molecular mutagenesis 2020-08, Vol.61 (7), p.752-766
Main Authors: Pereira, Catalina, Smolka, Marcus B., Weiss, Robert S., Brieño‐Enríquez, Miguel A.
Format: Article
Language:English
Subjects:
9‐1‐1 complex
Animals
Apoptosis
Ataxia
Ataxia telangiectasia
Ataxia Telangiectasia Mutated Proteins - genetics
ATR
Cell cycle
CHK1
CHK1 protein
Chromosomes
Damage
Deoxyribonucleic acid
DNA
DNA damage
DNA damage signaling
DNA repair
double‐stranded DNA break
Effectors
Gametes
Germ cells
homologous recombination
Humans
Kinases
Mammals
Mammals - genetics
Meiosis
Meiosis - genetics
Regulators
Repair
Scaffolds
Signal transduction
Signal Transduction - genetics
Signaling
synapsis
TOPBP1
Yeast
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Summary:In germ cells undergoing meiosis, the induction of double strand breaks (DSBs) is required for the generation of haploid gametes. Defects in the formation, detection, or recombinational repair of DSBs often result in defective chromosome segregation and aneuploidies. Central to the ability of meiotic cells to properly respond to DSBs are DNA damage response (DDR) pathways mediated by DNA damage sensor kinases. DDR signaling coordinates an extensive network of DDR effectors to induce cell cycle arrest and DNA repair, or trigger apoptosis if the damage is extensive. Despite their importance, the functions of DDR kinases and effector proteins during meiosis remain poorly understood and can often be distinct from their known mitotic roles. A key DDR kinase during meiosis is ataxia telangiectasia and Rad3‐related (ATR). ATR mediates key signaling events that control DSB repair, cell cycle progression, and meiotic silencing. These meiotic functions of ATR depend on upstream scaffolds and regulators, including the 9‐1‐1 complex and TOPBP1, and converge on many downstream effectors such as the checkpoint kinase CHK1. Here, we review the meiotic functions of the 9‐1‐1/TOPBP1/ATR/CHK1 signaling pathway during mammalian meiosis.
ISSN:0893-6692
1098-2280
DOI:10.1002/em.22401