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Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences.
Mol Cell Biol. 2003 Dec; 23(23):8820-8.MC

Abstract

End joining of double-strand breaks (DSBs) requires Ku proteins and frequently involves base pairing between complementary terminal sequences. To define the role of terminal base pairing in end joining, two oppositely oriented HO endonuclease cleavage sites separated by 2.0 kb were integrated into yeast chromosome III, where constitutive expression of HO endonuclease creates two simultaneous DSBs with no complementary end sequence. Lack of complementary sequence in their 3' single-strand overhangs facilitates efficient repair events distinctly different from when the 3' ends have a 4-bp sequence base paired in various ways to create 2- to 3-bp insertions. Repair of noncomplementary ends results in a set of nonrandom deletions of up to 302 bp, annealed by imperfect microhomology of about 8 to 10 bp at the junctions. This microhomology-mediated end joining (MMEJ) is Ku independent, but strongly dependent on Mre11, Rad50, and Rad1 proteins and partially dependent on Dnl4 protein. The MMEJ also occurs when Rad52 is absent, but the extent of deletions becomes more limited. The increased gamma ray sensitivity of rad1Delta rad52Delta yku70Delta strains compared to rad52Delta yku70Delta strains suggests that MMEJ also contributes to the repair of DSBs induced by ionizing radiation.

Authors+Show Affiliations

Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

14612421

Citation

Ma, Jia-Lin, et al. "Yeast Mre11 and Rad1 Proteins Define a Ku-independent Mechanism to Repair Double-strand Breaks Lacking Overlapping End Sequences." Molecular and Cellular Biology, vol. 23, no. 23, 2003, pp. 8820-8.
Ma JL, Kim EM, Haber JE, et al. Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol Cell Biol. 2003;23(23):8820-8.
Ma, J. L., Kim, E. M., Haber, J. E., & Lee, S. E. (2003). Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Molecular and Cellular Biology, 23(23), 8820-8.
Ma JL, et al. Yeast Mre11 and Rad1 Proteins Define a Ku-independent Mechanism to Repair Double-strand Breaks Lacking Overlapping End Sequences. Mol Cell Biol. 2003;23(23):8820-8. PubMed PMID: 14612421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. AU - Ma,Jia-Lin, AU - Kim,Eun Mi, AU - Haber,James E, AU - Lee,Sang Eun, PY - 2003/11/13/pubmed PY - 2003/12/17/medline PY - 2003/11/13/entrez SP - 8820 EP - 8 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 23 IS - 23 N2 - End joining of double-strand breaks (DSBs) requires Ku proteins and frequently involves base pairing between complementary terminal sequences. To define the role of terminal base pairing in end joining, two oppositely oriented HO endonuclease cleavage sites separated by 2.0 kb were integrated into yeast chromosome III, where constitutive expression of HO endonuclease creates two simultaneous DSBs with no complementary end sequence. Lack of complementary sequence in their 3' single-strand overhangs facilitates efficient repair events distinctly different from when the 3' ends have a 4-bp sequence base paired in various ways to create 2- to 3-bp insertions. Repair of noncomplementary ends results in a set of nonrandom deletions of up to 302 bp, annealed by imperfect microhomology of about 8 to 10 bp at the junctions. This microhomology-mediated end joining (MMEJ) is Ku independent, but strongly dependent on Mre11, Rad50, and Rad1 proteins and partially dependent on Dnl4 protein. The MMEJ also occurs when Rad52 is absent, but the extent of deletions becomes more limited. The increased gamma ray sensitivity of rad1Delta rad52Delta yku70Delta strains compared to rad52Delta yku70Delta strains suggests that MMEJ also contributes to the repair of DSBs induced by ionizing radiation. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/14612421/Yeast_Mre11_and_Rad1_proteins_define_a_Ku_independent_mechanism_to_repair_double_strand_breaks_lacking_overlapping_end_sequences_ L2 - https://journals.asm.org/doi/10.1128/MCB.23.23.8820-8828.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -