Balancing repair and tolerance of DNA damage caused by alkylating agents.

TitleBalancing repair and tolerance of DNA damage caused by alkylating agents.
Publication TypeJournal Article
Year of Publication2012
AuthorsFu, D, Calvo, JA, Samson, LD
JournalNat Rev Cancer
Volume12
Issue2
Pagination104-20
Date Published2012 Feb
ISSN1474-1768
KeywordsAlkylating Agents, Base Pair Mismatch, DNA Damage, DNA Repair, Humans
Abstract

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

DOI10.1038/nrc3185
Alternate JournalNat. Rev. Cancer
PubMed ID22237395
PubMed Central IDPMC3586545
Grant ListCA055042 / CA / NCI NIH HHS / United States
CA075576 / CA / NCI NIH HHS / United States
CA112967 / CA / NCI NIH HHS / United States
CA149261 / CA / NCI NIH HHS / United States
DP1 ES022576 / ES / NIEHS NIH HHS / United States
DP1 OD006422 / OD / NIH HHS / United States
DP1-OD006422 / OD / NIH HHS / United States
ES002109 / ES / NIEHS NIH HHS / United States
P30 ES002109 / ES / NIEHS NIH HHS / United States
R01 CA055042 / CA / NCI NIH HHS / United States
R01 CA075576 / CA / NCI NIH HHS / United States
R01 CA149261 / CA / NCI NIH HHS / United States
R01 CA149261-03 / CA / NCI NIH HHS / United States