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CTC1-mediated C-strand fill-in is an essential step in telomere length maintenance.

Abstract：

:To prevent progressive telomere shortening as a result of conventional DNA replication, new telomeric DNA must be added onto the chromosome end. The de novo DNA synthesis involves elongation of the G-rich strand of the telomere by telomerase. In human cells, the CST complex (CTC1-STN1-TEN1) also functions in telomere replication. CST first aids in duplication of the telomeric dsDNA. Then after telomerase has extended the G-rich strand, CST facilitates fill-in synthesis of the complementary C-strand. Here, we analyze telomere structure after disruption of human CTC1 and demonstrate that functional CST is essential for telomere length maintenance due to its role in mediating C-strand fill-in. Removal of CTC1 results in elongation of the 3΄ overhang on the G-rich strand. This leads to accumulation of RPA and telomeric DNA damage signaling. G-overhang length increases with time after CTC1 disruption and at early times net G-strand growth is apparent, indicating telomerase-mediated G-strand extension. In contrast, C-strand length decreases continuously, indicating a deficiency in C-strand fill-in synthesis. The lack of C-strand maintenance leads to gradual shortening of the telomeric dsDNA, similar to that observed in cells lacking telomerase. Thus, telomerase-mediated G-strand extension and CST-mediated C-strand fill-in are equally important for telomere length maintenance.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Feng X,Hsu SJ,Kasbek C,Chaiken M,Price CM

doi

10.1093/nar/gkx125

subject

Has Abstract

pub_date

2017-05-05 00:00:00

pages

4281-4293

issue

8

eissn

0305-1048

issn

1362-4962

pii

3038240

journal_volume

45

pub_type

杂志文章

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