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Biochemical Investigations Into the ...

Banerjee, Joydeep Kumar.

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Biochemical Investigations Into the Beyond 12/23 Rule of V(D)J Recombination.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Biochemical Investigations Into the Beyond 12/23 Rule of V(D)J Recombination./
作者:	Banerjee, Joydeep Kumar.
面頁冊數:	137 p.
附註:	Source: Dissertation Abstracts International, Volume: 74-10(E), Section: B.
Contained By:	Dissertation Abstracts International74-10B(E).
標題:	Health Sciences, Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3571958
ISBN:	9781303297564

Biochemical Investigations Into the Beyond 12/23 Rule of V(D)J Recombination.
Banerjee, Joydeep Kumar.

Biochemical Investigations Into the Beyond 12/23 Rule of V(D)J Recombination. - 137 p.

Source: Dissertation Abstracts International, Volume: 74-10(E), Section: B.

Thesis (Ph.D.)--Yale University, 2013.

The first step in creating a diverse repertoire of lymphocyte antigen receptors in jawed vertebrates is the somatic rearrangement of antigen receptor gene segments to form a single exon that codes for the binding region of the receptor. This process of highly regulated DNA cleavage and repair steps is known as V(D)J recombination. The cleavage phase of V(D)J recombination is catalyzed by a recombinase complex consisting of the lymphocyte-specific proteins recombination-activating gene (RAG)1 and 2, and a ubiquitously expressed DNA binding/bending protein HMGB1. Every gene segment is flanked by recombination signal sequences (RSSs) that direct recombinase binding and activity. Rearrangement only occurs between two gene segments with flanking RSSs that differ in spacer length (which can only be either 12 or 23 bp), a restriction called the 12/23 rule. At the Tcrb locus, Vbeta-to-Jbeta rearrangement is permitted by the 12/23 rule, but is not observed in vivo. This additional restriction is termed the Beyond 12/23 rule (B12/23 rule).

ISBN: 9781303297564Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Biochemical Investigations Into the Beyond 12/23 Rule of V(D)J Recombination.
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245 1 0 $a Biochemical Investigations Into the Beyond 12/23 Rule of V(D)J Recombination.
300 $a 137 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-10(E), Section: B.
500 $a Adviser: David G. Schatz.
502 $a Thesis (Ph.D.)--Yale University, 2013.
520 $a The first step in creating a diverse repertoire of lymphocyte antigen receptors in jawed vertebrates is the somatic rearrangement of antigen receptor gene segments to form a single exon that codes for the binding region of the receptor. This process of highly regulated DNA cleavage and repair steps is known as V(D)J recombination. The cleavage phase of V(D)J recombination is catalyzed by a recombinase complex consisting of the lymphocyte-specific proteins recombination-activating gene (RAG)1 and 2, and a ubiquitously expressed DNA binding/bending protein HMGB1. Every gene segment is flanked by recombination signal sequences (RSSs) that direct recombinase binding and activity. Rearrangement only occurs between two gene segments with flanking RSSs that differ in spacer length (which can only be either 12 or 23 bp), a restriction called the 12/23 rule. At the Tcrb locus, Vbeta-to-Jbeta rearrangement is permitted by the 12/23 rule, but is not observed in vivo. This additional restriction is termed the Beyond 12/23 rule (B12/23 rule).
520 $a Previous work showed that Vbeta RSSs do not recombine with Jbeta RSSs because Jbeta RSSs are functionally crippled in either nicking or synapsis. This result raised the question: how can crippled Jbeta RSSs recombine with Dbeta RSSs? I report here that the nicking of some Jbeta RSSs can be substantially stimulated by synapsis with a 3'Dbeta1 partner RSS. This result helps to reconcile disagreement in the field regarding the impact of synapsis on nicking. Furthermore, my data allow for the classification of Tcrb RSSs into two major categories: those that nick quickly and those that nick slowly in the absence of partner. Slow-nicking RSSs can be stimulated to nick more efficiently upon synapsis with an appropriate B12/23 partner and are either weakly stimulated or unchanged for nicking upon synapsis with an inappropriate partner. Fast-nicking RSSs are unexpectedly inhibited for nicking upon synapsis with an inappropriate partner, and can be stimulated, inhibited, or unchanged for nicking upon synapsis with an appropriate partner.
520 $a These observations imply that the RAG proteins exert fine control over every step of V(D)J cleavage at Tcrb and support an emerging model of B12/23 regulation centered on the 3'Dbeta1 23-RSS. My data also confirm previous findings regarding the coding flank's influence on nicking and reveal a novel role for the nonamer in reducing nicking.
590 $a School code: 0265.
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Biology, Molecular. $3 1017719
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690 $a 0487
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710 2 $a Yale University. $b Immunology. $3 2103694
773 0 $t Dissertation Abstracts International $g 74-10B(E).
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791 $a Ph.D.
792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3571958