PMID- 25795124
OWN - NLM
STAT- MEDLINE
DCOM- 20150528
LR  - 20210623
IS  - 1388-2139 (Electronic)
IS  - 1383-5742 (Print)
IS  - 1383-5742 (Linking)
VI  - 763
DP  - 2015 Jan-Mar
TI  - Crosstalk between translesion synthesis, Fanconi anemia network, and homologous 
      recombination repair pathways in interstrand DNA crosslink repair and development 
      of chemoresistance.
PG  - 258-66
LID - S1383-5742(14)00072-6 [pii]
LID - 10.1016/j.mrrev.2014.11.005 [doi]
AB  - Bifunctional alkylating and platinum based drugs are chemotherapeutic agents used 
      to treat cancer. These agents induce DNA adducts via formation of intrastrand or 
      interstrand (ICL) DNA crosslinks, and DNA lesions of the ICL type are 
      particularly toxic as they block DNA replication and/or DNA transcription. 
      However, the therapeutic efficacies of these drugs are frequently limited due to 
      the cancer cell's enhanced ability to repair and tolerate these toxic DNA 
      lesions. This ability to tolerate and survive the DNA damage is accomplished by a 
      set of specialized low fidelity DNA polymerases called translesion synthesis 
      (TLS) polymerases since high fidelity DNA polymerases are unable to replicate the 
      damaged DNA template. TLS is a crucial initial step in ICL repair as it 
      synthesizes DNA across the lesion thus preparing the damaged DNA template for 
      repair by the homologous recombination (HR) pathway and Fanconi anemia (FA) 
      network, processes critical for ICL repair. Here we review the molecular features 
      and functional roles of TLS polymerases, discuss the collaborative interactions 
      and cross-regulation of the TLS DNA damage tolerance pathway, the FA network and 
      the BRCA-dependent HRR pathway, and the impact of TLS hyperactivation on 
      development of chemoresistance. Finally, since TLS hyperactivation results from 
      overexpression of Rad6/Rad18 ubiquitinating enzymes (fundamental components of 
      the TLS pathway), increased PCNA ubiquitination, and/or increased recruitment of 
      TLS polymerases, the potential benefits of selectively targeting critical 
      components of the TLS pathway for enhancing anti-cancer therapeutic efficacy and 
      curtailing chemotherapy-induced mutagenesis are also discussed.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Haynes, Brittany
AU  - Haynes B
AD  - Department of Oncology, Wayne State University, 110 East Warren Avenue, Detroit, 
      MI 48201, United States; Karmanos Cancer Institute, Wayne State University, 110 
      East Warren Avenue, Detroit, MI 48201, United States.
FAU - Saadat, Nadia
AU  - Saadat N
AD  - Department of Oncology, Wayne State University, 110 East Warren Avenue, Detroit, 
      MI 48201, United States; Karmanos Cancer Institute, Wayne State University, 110 
      East Warren Avenue, Detroit, MI 48201, United States.
FAU - Myung, Brian
AU  - Myung B
AD  - Karmanos Cancer Institute, Wayne State University, 110 East Warren Avenue, 
      Detroit, MI 48201, United States.
FAU - Shekhar, Malathy P V
AU  - Shekhar MP
AD  - Department of Oncology, Wayne State University, 110 East Warren Avenue, Detroit, 
      MI 48201, United States; Karmanos Cancer Institute, Wayne State University, 110 
      East Warren Avenue, Detroit, MI 48201, United States; Department of Pathology, 
      Wayne State University, 110 East Warren Avenue, Detroit, MI 48201, United States. 
      Electronic address: shekharm@karmanos.org.
LA  - eng
GR  - R21 CA178117/CA/NCI NIH HHS/United States
GR  - R25 GM058905/GM/NIGMS NIH HHS/United States
GR  - T32 CA009531/CA/NCI NIH HHS/United States
GR  - CA178117/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20141120
PL  - Netherlands
TA  - Mutat Res Rev Mutat Res
JT  - Mutation research. Reviews in mutation research
JID - 101632211
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Fanconi Anemia Complementation Group Proteins)
RN  - 0 (Mutagens)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
SB  - IM
MH  - Antineoplastic Agents/adverse effects
MH  - DNA/*biosynthesis
MH  - DNA Damage
MH  - *DNA Repair
MH  - DNA-Directed DNA Polymerase/*metabolism
MH  - Drug Resistance, Neoplasm
MH  - Fanconi Anemia Complementation Group Proteins/*metabolism
MH  - Humans
MH  - Mutagens/adverse effects
MH  - Neoplasms/drug therapy/*genetics
MH  - Recombinational DNA Repair
MH  - Signal Transduction
PMC - PMC4369322
MID - NIHMS650749
OTO - NOTNLM
OT  - Interstrand DNA crosslinks
OT  - PCNA
OT  - Rad6
OT  - Ubiquitination
EDAT- 2015/03/22 06:00
MHDA- 2015/05/29 06:00
PMCR- 2016/01/01
CRDT- 2015/03/22 06:00
PHST- 2014/09/12 00:00 [received]
PHST- 2014/11/10 00:00 [revised]
PHST- 2014/11/11 00:00 [accepted]
PHST- 2015/03/22 06:00 [entrez]
PHST- 2015/03/22 06:00 [pubmed]
PHST- 2015/05/29 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - S1383-5742(14)00072-6 [pii]
AID - 10.1016/j.mrrev.2014.11.005 [doi]
PST - ppublish
SO  - Mutat Res Rev Mutat Res. 2015 Jan-Mar;763:258-66. doi: 
      10.1016/j.mrrev.2014.11.005. Epub 2014 Nov 20.