Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation

被引:56
作者
Sertic, Sarah [1 ]
Pizzi, Sara [1 ]
Cloney, Ross [2 ]
Lehmann, Alan R. [2 ]
Marini, Federica [1 ]
Plevani, Paolo [1 ]
Muzi-Falconi, Marco [1 ]
机构
[1] Univ Milan, Dipartimento Sci Biomol & Biotecnol, I-20133 Milan, Italy
[2] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England
基金
英国医学研究理事会;
关键词
local UV damage; UV lesion processing; ssDNA; ubiquitin; DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; MISMATCH REPAIR; FAMILY; RECOMBINATION; RECOGNITION; NUCLEASE; PROTEINS; COMPLEX; HEXO1;
D O I
10.1073/pnas.1108547108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
UV light induces DNA lesions, which are removed by nucleotide excision repair (NER). Exonuclease 1 (EXO1) is highly conserved from yeast to human and is implicated in numerous DNA metabolic pathways, including repair, recombination, replication, and telomere maintenance. Here we show that hEXO1 is involved in the cellular response to UV irradiation in human cells. After local UV irradiation, fluorescent-tagged hEXO1 localizes, together with NER factors, at the sites of damage in nonreplicating cells. hEXO1 accumulation requires XPF-dependent processing of UV-induced lesions and is enhanced by inhibition of DNA repair synthesis. In nonreplicating cells, depletion of hEXO1 reduces unscheduled DNA synthesis after UV irradiation, prevents ubiquitylation of histone H2A, and impairs activation of the checkpoint signal transduction cascade in response to UV damage. These findings reveal a key role for hEXO1 in the UV-induced DNA damage response linking NER to checkpoint activation in human cells.
引用
收藏
页码:13647 / 13652
页数:6
相关论文
共 32 条
[1]   Transcription-coupled repair and premature ageing [J].
Andressoo, JO ;
Hoeijmakers, JHJ .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2005, 577 (1-2) :179-194
[2]  
[Anonymous], 2005, DNA REPAIR MUTAGENES
[3]   Unwind and slow down: checkpoint activation by helicase and polymerase uncoupling [J].
Cortez, D .
GENES & DEVELOPMENT, 2005, 19 (09) :1007-1012
[4]   Molecular mechanism of nucleotide excision repair [J].
de Laat, WL ;
Jaspers, NGJ ;
Hoeijmakers, JHJ .
GENES & DEVELOPMENT, 1999, 13 (07) :768-785
[5]   Degradation of human exonuclease 1b upon DNA synthesis inhibition [J].
El-Shemerly, M ;
Janscak, P ;
Hess, D ;
Jiricny, J ;
Ferrari, S .
CANCER RESEARCH, 2005, 65 (09) :3604-3609
[6]   ATR-dependent pathways control hEXO1 stability in response to stalled forks [J].
El-Shemerly, Mahmoud ;
Hess, Daniel ;
Pyakurel, Aswin K. ;
Moselhy, Said ;
Ferrari, Stefano .
NUCLEIC ACIDS RESEARCH, 2008, 36 (02) :511-519
[7]   Physical and functional interactions between nucleotide excision repair and DNA damage checkpoint [J].
Giannattasio, M ;
Lazzaro, F ;
Longhese, MP ;
Plevani, P ;
Muzi-Falconi, M .
EMBO JOURNAL, 2004, 23 (02) :429-438
[8]   Exo1 Competes with Repair Synthesis, Converts NER Intermediates to Long ssDNA Gaps, and Promotes Checkpoint Activation [J].
Giannattasio, Michele ;
Follonier, Cindy ;
Tourriere, Helene ;
Puddu, Fabio ;
Lazzaro, Federico ;
Pasero, Philippe ;
Lopes, Massimo ;
Plevani, Paolo ;
Muzi-Falconi, Marco .
MOLECULAR CELL, 2010, 40 (01) :50-62
[9]   The DNA damage response: Ten years after [J].
Harper, J. Wade ;
Elledge, Stephen J. .
MOLECULAR CELL, 2007, 28 (05) :739-745
[10]   Aberrant mobility phenomena of the DNA repair protein XPA [J].
Iakoucheva, LM ;
Kimzey, AL ;
Masselon, CD ;
Smith, RD ;
Dunker, AK ;
Ackerman, EJ .
PROTEIN SCIENCE, 2001, 10 (07) :1353-1362