Premium
Human Stn1 protects telomere integrity by promoting efficient lagging‐strand telomere synthesis
Author(s) -
Huang Chenhui,
Dai Xueyu,
Chai Weihang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb92
Subject(s) - telomere , biology , lagging , telomerase , dna replication , microbiology and biotechnology , telomere binding protein , genome instability , dna polymerase , cell cycle , dna , genetics , dna damage , cell , dna binding protein , gene , transcription factor , medicine , pathology
Telomeres are critical for maintaining genome stability. The length of telomere is regulated by telomere specific and non‐specific proteins. Stn1, a component of Ctc1/Stn1/Ten1 complex, is known as DNA polymerase α‐accessory factor and plays an unclear role in telomere maintenance. In our studies, Stn1 depletion causes elongated G‐overhang and persistent ssDNA at G‐rich strand in both telomerase‐positive and negative cells. Stn1 depletion shows an increase of fragile telomeres in strands replicated by lagging strand synthesis, implicating that Stn1 is important in efficient replication of lagging strand telomeres. Consistently, BrdU incorporation into lagging telomeres is reduced when Stn1 is depleted. In addition, Stn1 depletion leads to rapid telomere shortening. Cell cycle‐regulated G‐overhang dynamics showed that deficiency of hStn1 delays and compromises C‐strand synthesis that occurs in the late S/G2 phase, leading to persistent lengthening of G‐overhangs at lagging daughter telomeres. We also found that Stn1 interacts with Polα throughout the cycle. ChIP experiments showed that Stn1 depletion results in increased and prolonged Polα association with telomeres, but does not affect the association of Pot1 with telomeres. Our data indicate a key role of Stn1 in telomere replication and maintenance. Supported by NIH R15GM099008 and American Cancer Society grant IRG‐77‐003‐32