共 45 条
Repair of a DNA-Protein Crosslink by Replication-Coupled Proteolysis
被引:182
作者:

Duxin, Julien P.
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

Dewar, James M.
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h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

Yardimci, Hasan
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h-index: 0
机构:
Imperial Canc Res Fund, Clare Hall Labs, London Res Inst, Canc Res UK, S Mimms EN6 3LD, Herts, England Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

Walter, Johannes C.
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h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
Howard Hughes Med Inst, Chevy Chase, MD USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
机构:
[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[2] Imperial Canc Res Fund, Clare Hall Labs, London Res Inst, Canc Res UK, S Mimms EN6 3LD, Herts, England
[3] Howard Hughes Med Inst, Chevy Chase, MD USA
来源:
关键词:
NUCLEOTIDE EXCISION-REPAIR;
XENOPUS EGG EXTRACTS;
FANCONI-ANEMIA;
HOMOLOGOUS RECOMBINATION;
MAMMALIAN-CELLS;
ABASIC SITES;
FORMALDEHYDE;
MECHANISM;
HELICASE;
PATHWAY;
D O I:
10.1016/j.cell.2014.09.024
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:
DNA-protein crosslinks (DPCs) are caused by environmental, endogenous, and chemotherapeutic agents and pose a severe threat to genome stability. We use Xenopus egg extracts to recapitulate DPC repair in vitro and show that this process is coupled to DNA replication. A DPC on the leading strand template arrests the replisome by stalling the CMG helicase. The DPC is then degraded on DNA, yielding a peptide-DNA adduct that is bypassed by CMG. The leading strand subsequently resumes synthesis, stalls again at the adduct, and then progresses past the adduct using DNA polymerase zeta. A DPC on the lagging strand template only transiently stalls the replisome, but it too is degraded, allowing Okazaki fragment bypass. Our experiments describe a versatile, proteolysis-based mechanism of S phase DPC repair that avoids replication fork collapse.
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页码:346 / 357
页数:12
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