p53 and p21 regulate error-prone DNA repair to yield a lower mutation load
Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence of multiple mutagenic DNA polymerases in mammals. These polymerases function in translesion DNA synthesis (TLS), an error-prone DNA repair pro...
Uloženo v:
| Vydáno v: | Molecular cell Ročník 22; číslo 3; s. 407 |
|---|---|
| Hlavní autoři: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
05.05.2006
|
| Témata: | |
| ISSN: | 1097-2765 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence of multiple mutagenic DNA polymerases in mammals. These polymerases function in translesion DNA synthesis (TLS), an error-prone DNA repair process that involves DNA synthesis across DNA lesions. We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency. This regulation may be mediated by binding of p21 to PCNA and via DNA damage-induced ubiquitination of PCNA, which is stimulated by p53 and p21. Loss of this regulation by inactivation of p53 or p21 causes an out of control lesion-bypass activity, which increases the mutational load and might therefore play a role in pathogenic processes caused by genetic instability. |
|---|---|
| AbstractList | Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence of multiple mutagenic DNA polymerases in mammals. These polymerases function in translesion DNA synthesis (TLS), an error-prone DNA repair process that involves DNA synthesis across DNA lesions. We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency. This regulation may be mediated by binding of p21 to PCNA and via DNA damage-induced ubiquitination of PCNA, which is stimulated by p53 and p21. Loss of this regulation by inactivation of p53 or p21 causes an out of control lesion-bypass activity, which increases the mutational load and might therefore play a role in pathogenic processes caused by genetic instability. Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence of multiple mutagenic DNA polymerases in mammals. These polymerases function in translesion DNA synthesis (TLS), an error-prone DNA repair process that involves DNA synthesis across DNA lesions. We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency. This regulation may be mediated by binding of p21 to PCNA and via DNA damage-induced ubiquitination of PCNA, which is stimulated by p53 and p21. Loss of this regulation by inactivation of p53 or p21 causes an out of control lesion-bypass activity, which increases the mutational load and might therefore play a role in pathogenic processes caused by genetic instability.Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence of multiple mutagenic DNA polymerases in mammals. These polymerases function in translesion DNA synthesis (TLS), an error-prone DNA repair process that involves DNA synthesis across DNA lesions. We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency. This regulation may be mediated by binding of p21 to PCNA and via DNA damage-induced ubiquitination of PCNA, which is stimulated by p53 and p21. Loss of this regulation by inactivation of p53 or p21 causes an out of control lesion-bypass activity, which increases the mutational load and might therefore play a role in pathogenic processes caused by genetic instability. |
| Author | Chaney, Stephen G Sevilya, Ziv Oren, Moshe Livneh, Zvi Geacintov, Nicholas Avkin, Sharon Toube, Leanne |
| Author_xml | – sequence: 1 givenname: Sharon surname: Avkin fullname: Avkin, Sharon organization: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel – sequence: 2 givenname: Ziv surname: Sevilya fullname: Sevilya, Ziv – sequence: 3 givenname: Leanne surname: Toube fullname: Toube, Leanne – sequence: 4 givenname: Nicholas surname: Geacintov fullname: Geacintov, Nicholas – sequence: 5 givenname: Stephen G surname: Chaney fullname: Chaney, Stephen G – sequence: 6 givenname: Moshe surname: Oren fullname: Oren, Moshe – sequence: 7 givenname: Zvi surname: Livneh fullname: Livneh, Zvi |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16678112$$D View this record in MEDLINE/PubMed |
| BookMark | eNo1T8lOwzAU9KGILvAHCPnELcFb7ORYFcqiCi5wjl7sF5TKiYOTCPXviUQ5jUYzmmVNFl3okJAbzlLOuL4_pm3wFn0qGNMpkykTYkFWnBUmEUZnS7IehiNjXGV5cUmWXGuTcy5W5LXPJIXO0V5wGvFr8jAixRhDTPo4t9CHt-0s9NBEOgZ6atA7CtSHH4y0nUYYm9DNFNwVuajBD3h9xg353D9-7J6Tw_vTy257SGzG5JjUslaSi9qwCgBdYYHJorLKFFpbLp2xoJjEDERWVxqNA5HbSuWcAa85KLEhd3-5877vCYexbJthPu-hwzANpTaFklLks_H2bJyqFl3Zx6aFeCr_34tf1nxdAg |
| CitedBy_id | crossref_primary_10_1182_blood_2009_10_248278 crossref_primary_10_1093_nar_gkn014 crossref_primary_10_1093_nar_gkp632 crossref_primary_10_3389_fimmu_2022_998975 crossref_primary_10_1093_nar_gkac545 crossref_primary_10_1002_em_22359 crossref_primary_10_1016_j_mrgentox_2021_503352 crossref_primary_10_1016_j_mrfmmm_2015_08_002 crossref_primary_10_1016_j_tiv_2009_05_009 crossref_primary_10_1371_journal_pgen_1002262 crossref_primary_10_1016_j_molimm_2021_08_005 crossref_primary_10_1038_s41467_023_44390_w crossref_primary_10_1093_nar_gkt475 crossref_primary_10_1038_ncomms6437 crossref_primary_10_1016_j_molimm_2010_05_291 crossref_primary_10_1128_MMBR_00034_08 crossref_primary_10_1158_0008_5472_CAN_14_2249 crossref_primary_10_1007_s00204_014_1430_4 crossref_primary_10_1074_jbc_M112_380998 crossref_primary_10_1128_MCB_00071_09 crossref_primary_10_4028_www_scientific_net_KEM_330_332_287 crossref_primary_10_1134_S0012496613060100 crossref_primary_10_3390_ijms12128513 crossref_primary_10_1002_stem_1177 crossref_primary_10_1016_j_molcel_2007_11_005 crossref_primary_10_1080_10409238_2019_1687420 crossref_primary_10_1134_S1990519X1702002X crossref_primary_10_1186_s13059_024_03451_z crossref_primary_10_1016_j_colsurfb_2006_11_003 crossref_primary_10_1016_j_fsi_2015_07_022 crossref_primary_10_1093_nar_gkae061 crossref_primary_10_1016_j_bbapap_2009_06_010 crossref_primary_10_1016_j_mam_2007_06_002 crossref_primary_10_1073_pnas_1216894110 crossref_primary_10_1111_php_13279 crossref_primary_10_1016_j_molimm_2011_01_004 crossref_primary_10_1038_s41420_025_02416_w crossref_primary_10_1093_nar_gkt1400 crossref_primary_10_1089_ars_2010_3673 crossref_primary_10_1134_S0006297910070138 crossref_primary_10_1016_j_biosystems_2010_07_005 crossref_primary_10_1186_s13059_018_1401_9 crossref_primary_10_1111_j_1600_0781_2008_00319_x crossref_primary_10_1093_nar_gkr596 crossref_primary_10_1073_pnas_1605828113 crossref_primary_10_3390_ijms22136957 crossref_primary_10_1042_BST0380104 crossref_primary_10_3390_ijms23137058 crossref_primary_10_1242_jcs_027730 crossref_primary_10_1016_j_molcel_2021_06_011 crossref_primary_10_1158_0008_5472_CAN_09_0627 crossref_primary_10_1038_cdd_2011_19 crossref_primary_10_1083_jcb_201408017 crossref_primary_10_1016_j_dnarep_2016_05_007 crossref_primary_10_1186_1476_4598_13_205 crossref_primary_10_1517_17460440903055032 crossref_primary_10_3390_genes11060593 crossref_primary_10_1038_onc_2011_237 crossref_primary_10_1016_j_mrfmmm_2015_06_006 crossref_primary_10_1016_j_mrfmmm_2012_11_002 crossref_primary_10_1038_emboj_2008_281 crossref_primary_10_1093_neuonc_now132 crossref_primary_10_1016_j_dnarep_2021_103230 crossref_primary_10_1038_cr_2011_34 crossref_primary_10_1093_nar_gkae078 crossref_primary_10_1016_j_febslet_2011_06_005 crossref_primary_10_1093_nar_gkab526 crossref_primary_10_1007_s00018_023_04919_0 crossref_primary_10_1016_S1016_8478_23_13956_2 crossref_primary_10_1371_journal_pone_0052348 crossref_primary_10_1002_jcp_30155 crossref_primary_10_1093_nar_gkp703 crossref_primary_10_1016_j_dnarep_2010_02_011 crossref_primary_10_1016_j_dnarep_2015_04_027 crossref_primary_10_7554_eLife_18020 crossref_primary_10_1038_sj_jid_5700988 crossref_primary_10_1093_nar_gks612 crossref_primary_10_1124_mol_111_074708 crossref_primary_10_1111_raq_12613 crossref_primary_10_4061_2010_761217 crossref_primary_10_7124_bc_000762 crossref_primary_10_1007_s10555_011_9329_5 crossref_primary_10_1016_j_dnarep_2009_02_005 crossref_primary_10_1083_jcb_201002124 crossref_primary_10_3390_genes15101271 crossref_primary_10_3390_cancers10080250 crossref_primary_10_1016_j_febslet_2011_04_044 crossref_primary_10_26508_lsa_202302230 crossref_primary_10_1073_pnas_0812548106 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.molcel.2006.03.022 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Biology |
| ExternalDocumentID | 16678112 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: CA099194 |
| GroupedDBID | --- --K -DZ -~X .55 .GJ 0R~ 0SF 123 1~5 2WC 3O- 4.4 457 4G. 53G 5RE 62- 6I. 7-5 AACTN AAEDT AAEDW AAFTH AAHBH AAIKJ AAKRW AAKUH AALRI AAMRU AAVLU AAXUO ABJNI ABMAC ABVKL ACGFO ACGFS ACNCT ADBBV ADEZE ADVLN AEFWE AENEX AEXQZ AFFNX AFTJW AGHFR AGKMS AITUG AKAPO AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF EJD F5P FCP FDB FEDTE FIRID HH5 HVGLF HZ~ IH2 IHE IXB J1W JIG KQ8 L7B M3Z M41 N9A NCXOZ NPM O-L O9- OK1 OZT P2P RCE RIG ROL RPZ SDG SES SSZ TR2 X7M 5VS 7X8 AAYWO ABDGV ACVFH ADCNI AEUPX AFPUW AIGII AKBMS AKYEP APXCP EFKBS |
| ID | FETCH-LOGICAL-c503t-f3f4312f70baaed9ca039bc47966c13d7ca403e5a25fb6e7da28cb4810a1f1a42 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 110 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000237618200011&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1097-2765 |
| IngestDate | Sun Nov 09 14:19:35 EST 2025 Sat Sep 28 07:45:42 EDT 2024 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 3 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c503t-f3f4312f70baaed9ca039bc47966c13d7ca403e5a25fb6e7da28cb4810a1f1a42 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://dx.doi.org/10.1016/j.molcel.2006.03.022 |
| PMID | 16678112 |
| PQID | 67943328 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_67943328 pubmed_primary_16678112 |
| PublicationCentury | 2000 |
| PublicationDate | 2006-05-05 |
| PublicationDateYYYYMMDD | 2006-05-05 |
| PublicationDate_xml | – month: 05 year: 2006 text: 2006-05-05 day: 05 |
| PublicationDecade | 2000 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Molecular cell |
| PublicationTitleAlternate | Mol Cell |
| PublicationYear | 2006 |
| SSID | ssj0014589 |
| Score | 2.2155795 |
| Snippet | Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 407 |
| SubjectTerms | Animals Cyclin-Dependent Kinase Inhibitor p21 - deficiency Cyclin-Dependent Kinase Inhibitor p21 - metabolism DNA - biosynthesis DNA Repair - genetics Gene Expression Regulation, Neoplastic Humans Mice Mice, Knockout Mutagenesis - genetics Mutation - genetics Proliferating Cell Nuclear Antigen - chemistry Proliferating Cell Nuclear Antigen - metabolism Protein Binding Protein Structure, Tertiary Tumor Suppressor Protein p53 - deficiency Tumor Suppressor Protein p53 - metabolism Ubiquitin - metabolism Ultraviolet Rays |
| Title | p53 and p21 regulate error-prone DNA repair to yield a lower mutation load |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/16678112 https://www.proquest.com/docview/67943328 |
| Volume | 22 |
| WOSCitedRecordID | wos000237618200011&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1JS8QwGA2jo-DFfRnXHLxG02ZpCoKIOohgmYPC3Eq2wsBMWzszwvx7ky54Eg9CKZSQNHx8TV7zXvIAuA4s57HxmiqbMUSVxkgKwZDhMVWKCzdpZbXZRJQkYjyORz1w1-2F8bLKbkysB2pTaL9Gfsv9SWYkFPflJ_KeUZ5bbQ001kCfOCDjBV3R-IdDoKw2wPMUKwojzrqNc7W6a1ZMtZ22ZAS5wd489zeIWU81w53_dXIXbLcQEz40ObEHejbfB5uN6eTqALyWjECZG1iGAawaK3oLbVUVFXKvyy18Sh5cQSknFVwUcOU1blDCqfdTg7Nlw927R2kOwcfw-f3xBbWOCkgzTBYoI5kDDGEWYSWlNbGWmMRK08j99OiAmEhLiollMmSZ4jYyMhRaURFgGWSBpOERWM9dR04A5JTzKLBYUFdHS-L5UqO4azemMafxAFx1IUpdxnoaQua2WM7TLkgDcNxEOS2bgzXSwDUpHAA8_bPuGdhq1kKYu85BP3Pfqr0AG_prMZlXl3UiuHsyevsGH5q8Fg |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=p53+and+p21+regulate+error-prone+DNA+repair+to+yield+a+lower+mutation+load&rft.jtitle=Molecular+cell&rft.au=Avkin%2C+Sharon&rft.au=Sevilya%2C+Ziv&rft.au=Toube%2C+Leanne&rft.au=Geacintov%2C+Nicholas&rft.date=2006-05-05&rft.issn=1097-2765&rft.volume=22&rft.issue=3&rft.spage=407&rft_id=info:doi/10.1016%2Fj.molcel.2006.03.022&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1097-2765&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1097-2765&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1097-2765&client=summon |