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PMID: 20039786 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

DNA interstrand crosslink repair in mammalian cells: step by step.

Critical reviews in biochemistry and molecular biology ·Vol. 45 ·No. 1 ·2010-02-00 ·Pages 23-49

Muniandy PA, Liu J, Majumdar A, Liu ST, Seidman MM

Abstract

Interstrand DNA crosslinks (ICLs) are formed by natural products of metabolism and by chemotherapeutic reagents. Work in E. coli identified a two cycle repair scheme involving incisions on one strand on either side of the ICL (unhooking) producing a gapped intermediate with the incised oligonucleotide attached to the intact strand. The gap is filled by recombinational repair or lesion bypass synthesis. The remaining monoadduct is then removed by nucleotide excision repair (NER). Despite considerable effort, our understanding of each step in mammalian cells is still quite limited. In part this reflects the variety of crosslinking compounds, each with distinct structural features, used by different investigators. Also, multiple repair pathways are involved, variably operative during the cell cycle. G(1) phase repair requires functions from NER, although the mechanism of recognition has not been determined. Repair can be initiated by encounters with the transcriptional apparatus, or a replication fork. In the case of the latter, the reconstruction of a replication fork, stalled or broken by collision with an ICL, adds to the complexity of the repair process. The enzymology of unhooking, the identity of the lesion bypass polymerases required to fill the first repair gap, and the functions involved in the second repair cycle are all subjects of active inquiry. Here we will review current understanding of each step in ICL repair in mammalian cells.

MeSH Terms
Animals Cell Cycle/genetics Cross-Linking Reagents/pharmacology DNA/drug effects,genetics,metabolism DNA Damage DNA Repair Fanconi Anemia/genetics,metabolism Humans Recombination, Genetic
Chemicals
Cross-Linking Reagents DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Muniandy Parameswary A
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Liu Jia
Majumdar Alokes
Liu Su-ting
Seidman Michael M
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Article Info
Journal
Critical reviews in biochemistry and molecular biology
Abbr.
Crit Rev Biochem Mol Biol
ISSN
1549-7798
DOI
10.3109/10409230903501819
Published
2010-02-00
Pages
23-49
Language
English
Region
England
NLM ID
8903774
PMCID
PMC2824768
Subset
IM
Grants
Intramural NIH HHS · Z01 AG000746 · United States
Intramural NIH HHS · Z01 AG000746-02 · United States
NIA NIH HHS · AG000746-02 · United States
External Links
PubMed source DOI: 10.3109/10409230903501819 PMC Full Text View journal details
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