Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it

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Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it

Telomeric repeat binding factor 2 (TRF2) folds human telomeres into loops to prevent unwanted DNA repair and chromosome end-joining. The N-terminal basic domain of TRF2 (B-domain) protects the telomeric displacement loop (D-loop) from cleavage by endonucleases. Repressor activator protein 1 (Rap1) binds TRF2 and improves telomeric DNA recognition. We found that the B-domain of TRF2 stabilized t...

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TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions

Repressor/activator protein 1 (RAP1) is a highly conserved telomere-interacting protein. Yeast Rap1 protects telomeres from non-homologous end joining (NHEJ), plays important roles in telomere length control and is involved in transcriptional gene regulation. However, a role for mammalian RAP1 in telomere end protection remains controversial. Here we present evidence that mammalian RAP1 is esse...

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TRF2 Recruits RTEL1 to Telomeres in S Phase to Promote T-Loop Unwinding

The helicase RTEL1 promotes t-loop unwinding and suppresses telomere fragility to maintain the integrity of vertebrate telomeres. An interaction between RTEL1 and PCNA is important to prevent telomere fragility, but how RTEL1 engages with the telomere to promote t-loop unwinding is unclear. Here, we establish that the shelterin protein TRF2 recruits RTEL1 to telomeres in S phase, which is requi...

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Human Rap1 modulates TRF2 attraction to telomeric DNA

More than two decades of genetic research have identified and assigned main biological functions of shelterin proteins that safeguard telomeres. However, a molecular mechanism of how each protein subunit contributes to the protecting function of the whole shelterin complex remains elusive. Human Repressor activator protein 1 (Rap1) forms a multifunctional complex with Telomeric Repeat binding F...

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Telomeric protein TRF2 protects Holliday junctions with telomeric arms from displacement by the Werner syndrome helicase

WRN protein loss causes Werner syndrome (WS), which is characterized by premature aging as well as genomic and telomeric instability. WRN prevents telomere loss, but the telomeric protein complex must regulate WRN activities to prevent aberrant telomere processing. Telomere-binding TRF2 protein inhibits telomere t-loop deletion by blocking Holliday junction (HJ) resolvase cleavage activity, but...

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ژورنال

عنوان ژورنال: Nucleic Acids Research

سال: 2017

ISSN: 0305-1048,1362-4962

DOI: 10.1093/nar/gkx968