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Function, replication and structure of the mammalian telomere

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Abstract

Telomeres are specialized structures at the ends of linear chromosomes that were originally defined functionally based on observations first by Muller (1938) and subsequently by McClintock (1941) that naturally occurring chromosome ends do not behave as double-stranded DNA breaks, in spite of the fact that they are the physical end of a linear, duplex DNA molecule. Double-stranded DNA breaks are highly unstable entities, being susceptible to nucleolytic attack and giving rise to chromosome rearrangements through end-to-end fusions and recombination events. In contrast, telomeres confer stability upon chromosome termini, as evidenced by the fact that chromosomes are extraordinarily stable through multiple cell divisions and even across evolutionary time. This protective function of telomeres is due to the formation of a nucleoprotein complex that sequesters the end of the DNA molecule, rendering it inaccessible to nucleases and recombinases as well as preventing the telomere from activating the DNA damage checkpoint pathways. The capacity of a functional end-protective complex to form is dependent upon maintenance of sufficient telomeric DNA. We have learned a great deal about telomere structure and how this specialized nucleoprotein complex confers stability on chromosome ends since the original observations that defined telomeres were made. This review summarizes our current understanding of mammalian telomere replication, structure and function.

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Abbreviations

53BP1:

TP53 binding protein 1

ATM:

Ataxia telangiectasia mutated

BRCT:

BRCA1 carboxy terminal

DAT:

Dissociates activities of telomerase

DNA-PKcs:

DNA-dependent protein kinase catalytic subunit

EST1/hEST1:

Ever shorter telomeres 1

MRN:

MRE11/RAD50/NBS1 complex

PARP:

Poly ADP-ribose polymerase

PINX1:

Pin2/TRF1 interacting protein

POT1:

Protection of telomeres 1

RAD54:

radiation senstitivity mutant 54

hRAP1:

human homologue of S. cerevisiae Repressor Activator Protein 1

hTERT/mTERT:

human and mouse homologues of telomerase reverse transcriptase catalytic subunit

hTERTα:

alternatively spliced inhibitory form of hTERT

TIN2:

TRF1 interacting protein 2

TPE:

Telomeric position effect

hTR/mTR:

Human and mouse homologues telomerase template RNA subunit

TRF1:

TTAGGG-repeat binding factor 1

TRF2:

TTAGGG-repeat binding factor 2

XPF-ERCC1:

Xeroderma pigmentosum complementation group F/Excision repair cross-complementing 1

XRCC4:

X-ray-complementing Chinese hamster gene 4.

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  1. Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Dominique Broccoli

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  1. Dominique Broccoli
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Broccoli, D. Function, replication and structure of the mammalian telomere. Cytotechnology 45, 3–12 (2004). https://doi.org/10.1007/s10616-004-5120-6

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