Pot1 promotes telomere DNA replication via the Stn1-Ten1 complex in fission yeast

被引:2
|
作者
Borges, Pamela C. Carvalho [1 ]
Bouabboune, Chainez [2 ]
Escandell, Jose Miguel [1 ,4 ]
Matmati, Samah [2 ]
Coulon, Stephane [1 ,2 ]
Ferreira, Miguel Godinho [1 ,3 ]
机构
[1] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal
[2] Aix Marseille Univ, CNRS, Inst Paoli Calmettes, INSERM,CRCM,Equipe Labellisee Ligue Natl Canc, F-13009 Marseille, France
[3] Inst Res Canc & Aging Nice IRCAN, INSERM, CNRS, U1081,UMR7284, F-06107 Nice, France
[4] Inst Biol Expt & Tecnolog, IBET, Apartado 12, P-2780901 Oeiras, Portugal
关键词
HUMAN CST; PROTECTS TELOMERES; DUPLEX REPLICATION; DAMAGE RESPONSE; FILL-IN; END; CHECKPOINT; TPZ1(TPP1); TEL1(ATM); EFFICIENT;
D O I
10.1093/nar/gkad1036
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Telomeres are nucleoprotein complexes that protect the chromosome-ends from eliciting DNA repair while ensuring their complete duplication. Pot1 is a subunit of telomere capping complex that binds to the G-rich overhang and inhibits the activation of DNA damage checkpoints. In this study, we explore new functions of fission yeast Pot1 by using a pot1-1 temperature sensitive mutant. We show that pot1 inactivation impairs telomere DNA replication resulting in the accumulation of ssDNA leading to the complete loss of telomeric DNA. Recruitment of Stn1 to telomeres, an auxiliary factor of DNA lagging strand synthesis, is reduced in pot1-1 mutants and overexpression of Stn1 rescues loss of telomeres and cell viability at restrictive temperature. We propose that Pot1 plays a crucial function in telomere DNA replication by recruiting Stn1-Ten1 and Pol alpha-primase complex to telomeres via Tpz1, thus promoting lagging-strand DNA synthesis at stalled replication forks. [GRAPHICS] .
引用
收藏
页码:12325 / 12336
页数:12
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