Abstract:
:The Werner syndrome protein (WRN) suppresses the loss of telomeres replicated by lagging-strand synthesis by a yet to be defined mechanism. Here, we show that whereas either WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase δ progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage, a critical step in Okazaki fragment maturation, at these sequences. Helicase activity, as well as the conserved winged-helix (WH) motif and the helicase and RNase D C-terminal (HRDC) domain play important but distinct roles in this process. Remarkably, WRN also influences the formation of FEN1 cleavage products during strand displacement on a nontelomeric substrate, suggesting that WRN recruitment and cooperative interaction with FEN1 during lagging-strand synthesis may serve to regulate sequential strand displacement and flap cleavage at other genomic sites. These findings define a biochemical context for the physiological role of WRN in maintaining genetic stability.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Li B,Reddy S,Comai Ldoi
10.1128/MCB.00560-16subject
Has Abstractpub_date
2017-01-19 00:00:00issue
3eissn
0270-7306issn
1098-5549pii
MCB.00560-16journal_volume
37pub_type
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