Processing of Damaged DNA Ends for Double-Strand Break Repair in Mammalian Cells
Author
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-12-04
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Abstract EN
Most DNA double-strand breaks (DSBs) formed in a natural environment have chemical modifications at or near the ends that preclude direct religation and require removal or other processing so that rejoining can proceed.
Free radical-mediated DSBs typically bear unligatable 3′-phosphate or 3′-phosphoglycolate termini and often have oxidized bases and/or abasic sites near the break.
Topoisomerase-mediated DSBs are blocked by covalently bound peptide fragments of the topoisomerase.
Enzymes capable of resolving damaged ends include polynucleotide kinase/phosphatase, which restores missing 5′-phosphates and removes 3′-phosphates; tyrosyl-DNA phosphodiesterases I and II (TDP1 and TDP2), which remove peptide fragments of topoisomerases I and II, respectively; and the Artemis and Metnase endonucleases, which can trim damaged overhangs of diverse structure.
TDP1 as well as APE1 can remove 3′-phosphoglycolates and other 3′ blocks, while CtIP appears to provide an alternative pathway for topoisomerase II fragment removal.
Ku, a core DSB joining protein, can cleave abasic sites near DNA ends.
The downstream processes of patching and ligation are tolerant of residual damage and can sometimes proceed without complete damage removal.
Despite these redundant pathways for resolution, damaged ends appear to be a significant barrier to rejoining, and their resolution may be a rate-limiting step in repair of some DSBs.
American Psychological Association (APA)
Povirk, Lawrence F.. 2012. Processing of Damaged DNA Ends for Double-Strand Break Repair in Mammalian Cells. ISRN Molecular Biology،Vol. 2012, no. 2012, pp.1-16.
https://search.emarefa.net/detail/BIM-464502
Modern Language Association (MLA)
Povirk, Lawrence F.. Processing of Damaged DNA Ends for Double-Strand Break Repair in Mammalian Cells. ISRN Molecular Biology No. 2012 (2012), pp.1-16.
https://search.emarefa.net/detail/BIM-464502
American Medical Association (AMA)
Povirk, Lawrence F.. Processing of Damaged DNA Ends for Double-Strand Break Repair in Mammalian Cells. ISRN Molecular Biology. 2012. Vol. 2012, no. 2012, pp.1-16.
https://search.emarefa.net/detail/BIM-464502
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-464502