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Telomere homeostasis in mammalian germ cells: a review

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Abstract

Telomeres protect against genome instability and participate in chromosomal movements during gametogenesis, especially in meiosis. Thus, maintaining telomere structure and telomeric length is essential to both cell integrity and the production of germ cells. As a result, alteration of telomere homeostasis in the germ line may result in the generation of aneuploid gametes or gametogenesis disruption, triggering fertility problems. In this work, we provide an overview on fundamental aspects of the literature regarding the organization of telomeres in mammalian germ cells, paying special attention to telomere structure and function, as well as the maintenance of telomeric length during gametogenesis. Moreover, we discuss the different roles recently described for telomerase and TERRA in maintaining telomere functionality. Finally, we review how new findings in the field of reproductive biology underscore the role of telomere homeostasis as a potential biomarker for infertility. Overall, we anticipate that the study of telomere stability and equilibrium will contribute to improve diagnoses of patients; assess the risk of infertility in the offspring; and in turn, find new treatments.

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Abbreviations

ALT:

Alternative lengthening of telomere

COs:

Crossovers

DSBs:

Double-strand breaks

IVF:

In vitro fertilization

KASH:

Klarsicht/ANC-1/syne/homology

KASH5:

KASH domain-containing protein 5

LINC:

Linker of nucleoskeleton and cytoskeleton

NE:

Nuclear envelope

POT1:

Protection of telomeres 1

RAP1:

Repressor and activator protein 1

SMC1β:

Structural maintenance of chromosomes 1β

STAG3:

Stroma antigen 3

SUN:

Sad-1/UNC-84

SUN1:

SUN domain-containing protein 1

SUN2:

SUN domain-containing protein 2

TERB1:

Telomere repeat-binding bouquet formation protein 1

TERRA:

Telomeric repeat-containing RNA

TERT:

Telomerase reverse transcriptase

TIN2:

TRF1-interacting nuclear factor 2

TPP1:

TIN2- and POT1-interacting nuclear protein 1

TR:

Telomerase RNA component

TRAP:

Telomeric repeat amplification protocol

TRF1:

Telomeric repeat-binding factor 1

TRF2:

Telomeric repeat-binding factor 2

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Acknowledgments

R.R.-V. was the recipient of a PIF fellowship from the Universitat Autònoma de Barcelona. This work was partially funded by the Generalitat de Catalunya (2009SGR1107).

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Correspondence to Montserrat Garcia-Caldés or Aurora Ruiz-Herrera.

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R.R.-V. declares that she has no conflict of interest. M.G.-C. declares that she has no conflict of interest. A.R.-H. declares that she has no conflict of interest.

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This article is part of a Special Issue on “Recent advances in meiotic chromosome structure, recombination, and segregation” edited by Marco Barchi, Paula Cohen, and Scott Keeney

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Reig-Viader, R., Garcia-Caldés, M. & Ruiz-Herrera, A. Telomere homeostasis in mammalian germ cells: a review. Chromosoma 125, 337–351 (2016). https://doi.org/10.1007/s00412-015-0555-4

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